Signal transduction via platelet-derived growth factor receptors.

Platelet-derived growth factor (PDGF) exerts its stimulatory effects on cell growth and motility by binding to two related protein tyrosine kinase receptors. Ligand binding induces receptor dimerization and autophosphorylation, allowing binding and activation of cytoplasmic SH2-domain containing signal transduction molecules. Thereby, a number of different signaling pathways are initiated leading to cell growth, actin reorganization migration and differentiation. Recent observations suggest that extensive cross-talk occurs between different signaling pathways, and that stimulatory signals are modulated by inhibitory signals arising in parallel.

[1]  L. Heasley,et al.  Analysis of mutant platelet-derived growth factor receptors expressed in PC12 cells identifies signals governing sodium channel induction during neuronal differentiation , 1997, Molecular and cellular biology.

[2]  C. Heldin,et al.  Platelet-derived growth factor (PDGF)-induced actin rearrangement is deregulated in cells expressing a mutant Y778F PDGF beta-receptor. , 1998, Journal of cell science.

[3]  P. Phillips,et al.  Two different subunits associate to create isoform-specific platelet-derived growth factor receptors. , 1989, The Journal of biological chemistry.

[4]  A. Ullrich,et al.  Inhibition of platelet-derived growth factor-mediated signal transduction and tumor growth by N-[4-(trifluoromethyl)-phenyl]5-methylisoxazole-4-carboxamide. , 1997, Clinical cancer research : an official journal of the American Association for Cancer Research.

[5]  M. Tanimoto,et al.  Fusion of the platelet-derived growth factor receptor beta to a novel gene CEV14 in acute myelogenous leukemia after clonal evolution. , 1997, Blood.

[6]  C. Kahn,et al.  A cascade of tyrosine autophosphorylation in the beta-subunit activates the phosphotransferase of the insulin receptor. , 1988, The Journal of biological chemistry.

[7]  C. Nobes,et al.  Rho, Rac, and Cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia , 1995, Cell.

[8]  T. Pawson,et al.  Drosophila Photoreceptor Axon Guidance and Targeting Requires the Dreadlocks SH2/SH3 Adapter Protein , 1996, Cell.

[9]  L. Heasley,et al.  The beta-PDGF receptor induces neuronal differentiation of PC12 cells. , 1992, Molecular biology of the cell.

[10]  C. Heldin,et al.  Platelet-derived growth factor (PDGF) in oncogenesis: development of a vascular connective tissue stroma in xenotransplanted human melanoma producing PDGF-BB. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[11]  M. Koegl,et al.  Sequence Requirements for Binding of Src Family Tyrosine Kinases to Activated Growth Factor Receptors (*) , 1995, The Journal of Biological Chemistry.

[12]  T. Golub,et al.  The TEL/platelet-derived growth factor β receptor (PDGFβR) fusion in chronic myelomonocytic leukemia is a transforming protein that self-associates and activates PDGFβR kinase-dependent signaling pathways , 1996 .

[13]  M. Pazin,et al.  A functional soluble extracellular region of the platelet-derived growth factor (PDGF) beta-receptor antagonizes PDGF-stimulated responses. , 1991, The Journal of biological chemistry.

[14]  F. Grinnell,et al.  Decreased level of PDGF-stimulated receptor autophosphorylation by fibroblasts in mechanically relaxed collagen matrices , 1993, The Journal of cell biology.

[15]  U. Hellman,et al.  Identification of two C‐terminal autophosphorylation sites in the PDGF beta‐receptor: involvement in the interaction with phospholipase C‐gamma. , 1992, The EMBO journal.

[16]  R. Dolle,et al.  5,7-Dimethoxy-3-(4-pyridinyl)quinoline is a potent and selective inhibitor of human vascular beta-type platelet-derived growth factor receptor tyrosine kinase. , 1994, Journal of medicinal chemistry.

[17]  E. Krebs,et al.  cAMP- and rapamycin-sensitive regulation of the association of eukaryotic initiation factor 4E and the translational regulator PHAS-I in aortic smooth muscle cells. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[18]  S. Ryu,et al.  Activation of phospholipase D induced by platelet-derived growth factor is dependent upon the level of phospholipase C-gamma 1. , 1994, The Journal of biological chemistry.

[19]  Jonathan A. Cooper,et al.  Autophosphorylation of the PDGF receptor in the kinase insert region regulates interactions with cell proteins , 1989, Cell.

[20]  M. Kasuga,et al.  Phosphatidylinositol 3-Kinase-independent Signal Transduction Pathway for Platelet-derived Growth Factor-induced Chemotaxis* , 1996, The Journal of Biological Chemistry.

[21]  E. Krebs,et al.  Protein kinase A antagonizes platelet-derived growth factor-induced signaling by mitogen-activated protein kinase in human arterial smooth muscle cells. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[22]  C. Leslie,et al.  The mitogen-activated protein kinase pathway can mediate growth inhibition and proliferation in smooth muscle cells. Dependence on the availability of downstream targets. , 1997, The Journal of clinical investigation.

[23]  M. Jaumann,et al.  On the structure of platelet-derived growth factor AA: C-terminal processing, epitopes, and characterization of cysteine residues. , 1991, Biochemistry.

[24]  S. Hanks,et al.  Focal adhesion protein-tyrosine kinase phosphorylated in response to cell attachment to fibronectin. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[25]  R. Senior,et al.  PDGF AA homodimers are potent chemoattractants for fibroblasts and neutrophils, and for monocytes activated by lymphocytes or cytokines. , 1992, Biochemical and biophysical research communications.

[26]  Charles Eigenbrot,et al.  Crystal Structure at 1.7 Å Resolution of VEGF in Complex with Domain 2 of the Flt-1 Receptor , 1997, Cell.

[27]  J. Massagué,et al.  Cyclic AMP-induced G1 phase arrest mediated by an inhibitor (p27 Kip1 ) of cyclin-dependent kinase 4 activation , 1994, Cell.

[28]  C. Damsky,et al.  Requirement of the NPXY motif in the integrin beta 3 subunit cytoplasmic tail for melanoma cell migration in vitro and in vivo , 1995, The Journal of cell biology.

[29]  S. Aaronson,et al.  Differences in substrate specificities of alpha and beta platelet-derived growth factor (PDGF) receptors. Correlation with their ability to mediate PDGF transforming functions. , 1993, The Journal of biological chemistry.

[30]  R. Mooney,et al.  Activation of phosphatidylinositol-3-kinase by platelet-derived growth factor and insulin-like growth factor-1 is inhibited by a transmembrane phosphotyrosine phosphatase. , 1993, The Journal of biological chemistry.

[31]  G. M. Briggs,et al.  In vitro characterization of a novel series of platelet-derived growth factor receptor tyrosine kinase inhibitors. , 1996, Biochemical pharmacology.

[32]  B. Zetter,et al.  Platelet-derived Growth Factor and Fibronectin-stimulated Migration Are Differentially Regulated by the Rac and Extracellular Signal-regulated Kinase Pathways* , 1997, The Journal of Biological Chemistry.

[33]  D. Morrison,et al.  Platelet-derived growth factor (PDGF)-dependent association of phospholipase C-gamma with the PDGF receptor signaling complex , 1990, Molecular and cellular biology.

[34]  S. Shoelson,et al.  Human GRB-IRbeta/GRB10. Splice variants of an insulin and growth factor receptor-binding protein with PH and SH2 domains. , 1997, The Journal of biological chemistry.

[35]  G. Bokoch,et al.  Interaction of the Nck Adapter Protein with p21-activated Kinase (PAK1)* , 1996, Journal of Biological Chemistry.

[36]  K Seyama,et al.  Localization of platelet-derived growth factor and insulin-like growth factor I in the fibrotic lung. , 1995, American journal of respiratory and critical care medicine.

[37]  S. Spiegel,et al.  Divergence in Signal Transduction Pathways of Platelet-derived Growth Factor (PDGF) and Epidermal Growth Factor (EGF) Receptors , 1997, The Journal of Biological Chemistry.

[38]  C. Heldin,et al.  Reversion of autocrine transformation by a dominant negative platelet-derived growth factor mutant , 1993, Molecular and cellular biology.

[39]  M. Reidy,et al.  Inhibition of neointimal smooth muscle accumulation after angioplasty by an antibody to PDGF , 1991, Science.

[40]  H. Abboud.  Growth factors in glomerulonephritis. , 1993, Kidney international.

[41]  E. Krebs,et al.  Sphingosine-1-phosphate inhibits PDGF-induced chemotaxis of human arterial smooth muscle cells: spatial and temporal modulation of PDGF chemotactic signal transduction , 1995, The Journal of cell biology.

[42]  C. Der,et al.  Activation of Rac1, RhoA, and mitogen-activated protein kinases is required for Ras transformation , 1995, Molecular and cellular biology.

[43]  P. D’Eustachio,et al.  The SH2 domain protein GRB‐7 is co‐amplified, overexpressed and in a tight complex with HER2 in breast cancer. , 1994, The EMBO journal.

[44]  J. Parsons,et al.  pp125FAK a structurally distinctive protein-tyrosine kinase associated with focal adhesions. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[45]  S. Courtneidge,et al.  Association between the PDGF receptor and members of the src family of tyrosine kinases , 1990, Cell.

[46]  C. Heldin,et al.  Ligand-induced dimerization of growth factor receptors: variations on the theme. , 1996, Cytokine & growth factor reviews.

[47]  W. Kenney,et al.  Disulfide bonds in recombinant human platelet-derived growth factor BB dimer: characterization of intermolecular and intramolecular disulfide linkages. , 1993, Biochemistry.

[48]  G M Sanderson,et al.  Cloning and Characterization of GRB14, a Novel Member of the GRB7 Gene Family (*) , 1996, The Journal of Biological Chemistry.

[49]  J. Brugge,et al.  Integrins and signal transduction pathways: the road taken. , 1995, Science.

[50]  P. Hawkins,et al.  Activation of the small GTP-binding proteins rho and rac by growth factor receptors. , 1995, Journal of cell science.

[51]  R. Fenstermaker,et al.  A cationic region of the platelet-derived growth factor (PDGF) A-chain (Arg159-Lys160-Lys161) is required for receptor binding and mitogenic activity of the PDGF-AA homodimer. , 1993, The Journal of biological chemistry.

[52]  Anne J. Ridley,et al.  The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors , 1992, Cell.

[53]  A. Ullrich,et al.  Effect of phospholipase C-gamma overexpression on PDGF-induced second messengers and mitogenesis. , 1990, Science.

[54]  A. Kazlauskas,et al.  Activation of phospholipase C-gamma is necessary for stimulation of phospholipase D by platelet-derived growth factor. , 1994, The Journal of biological chemistry.

[55]  A. Ullrich,et al.  Inhibition of glioma cell growth by a truncated platelet-derived growth factor-beta receptor. , 1994, The Journal of biological chemistry.

[56]  C. Walsh,et al.  Activation of the SH2-containing phosphotyrosine phosphatase SH-PTP2 by its binding site, phosphotyrosine 1009, on the human platelet-derived growth factor receptor. , 1993, The Journal of biological chemistry.

[57]  S. Soker,et al.  Excess early signaling activity inhibits cellular chemotaxis toward PDGF-BB. , 1994, Oncogene.

[58]  A. Cuadrado,et al.  Overexpression of phospholipase C-gamma in NIH 3T3 fibroblasts results in increased phosphatidylinositol hydrolysis in response to platelet-derived growth factor and basic fibroblast growth factor , 1990, Molecular and cellular biology.

[59]  R F Doolittle,et al.  Simian sarcoma virus onc gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor. , 1983, Science.

[60]  C. Heldin,et al.  Identification of a hydrophobic region in the carboxyl terminus of the platelet-derived growth factor beta-receptor which is important for ligand-mediated endocytosis. , 1991, The Journal of biological chemistry.

[61]  G. Mills,et al.  Src Kinase Activity Is Regulated by the SHP-1 Protein-tyrosine Phosphatase* , 1997, The Journal of Biological Chemistry.

[62]  H. Ohnishi,et al.  A new approach to the treatment of atherosclerosis and trapidil as an antagonist to platelet-derived growth factor. , 1981, Life sciences.

[63]  J. Schlessinger,et al.  Activation of phospholipase Cγ by PI 3‐kinase‐induced PH domain‐mediated membrane targeting , 1998 .

[64]  R. Reed,et al.  A novel physiological function for platelet‐derived growth factor‐BB in rat dermis. , 1996, The Journal of physiology.

[65]  T. Pawson,et al.  Signaling through scaffold, anchoring, and adaptor proteins. , 1997, Science.

[66]  S. Coughlin,et al.  Role of phosphatidylinositol kinase in PDGF receptor signal transduction. , 1989, Science.

[67]  F. McCormick,et al.  Dual role of phosphatidylinositol-3,4,5-trisphosphate in the activation of protein kinase B. , 1997, Science.

[68]  M. Berridge.  Inositol trisphosphate and calcium signalling , 1993, Nature.

[69]  D. Pot,et al.  A specific product of phosphatidylinositol 3-kinase directly activates the protein kinase Akt through its pleckstrin homology domain , 1997, Molecular and cellular biology.

[70]  Richard A.F. Clark,et al.  The Molecular and Cellular Biology of Wound Repair , 2012, Springer US.

[71]  J. Khire,et al.  Ligand-induced dimerization of the platelet-derived growth factor receptor. Monomer-dimer interconversion occurs independent of receptor phosphorylation. , 1989, The Journal of biological chemistry.

[72]  S. Pyne,et al.  Sphingomyelin-derived lipids differentially regulate the extracellular signal-regulated kinase 2 (ERK-2) and c-Jun N-terminal kinase (JNK) signal cascades in airway smooth muscle. , 1996, European journal of biochemistry.

[73]  C. Heldin,et al.  Grb7 is a Downstream Signaling Component of Platelet-derived Growth Factor α- and β-Receptors* , 1996, The Journal of Biological Chemistry.

[74]  O. Bernard,et al.  A domain of TEL conserved in a subset of ETS proteins defines a specific oligomerization interface essential to the mitogenic properties of the TEL–PDGFRβ oncoprotein , 1997, The EMBO journal.

[75]  C. Heldin,et al.  Identification of a peptide antagonist for platelet-derived growth factor. , 1992, The Journal of biological chemistry.

[76]  C. Heldin,et al.  A tyrosine residue in the juxtamembrane segment of the platelet-derived growth factor beta-receptor is critical for ligand-mediated endocytosis. , 1994, The Journal of biological chemistry.

[77]  M. Heidaran,et al.  Characterization of baculovirus-expressed human alpha and beta platelet-derived growth factor receptors. , 1992, Biochemistry.

[78]  M. Kasuga,et al.  Activation of phosphoinositide 3-kinase is required for PDGF-stimulated membrane ruffling , 1994, Current Biology.

[79]  B R Johansson,et al.  Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. , 1997, Science.

[80]  G. Panayotou,et al.  Interaction of the p85 subunit of PI 3‐kinase and its N‐terminal SH2 domain with a PDGF receptor phosphorylation site: structural features and analysis of conformational changes. , 1992, The EMBO journal.

[81]  Zhong-Qing Shi,et al.  The Shp-2 Tyrosine Phosphatase Has Opposite Effects in Mediating the Activation of Extracellular Signal-regulated and c-Jun NH2-terminal Mitogen-activated Protein Kinases* , 1998, The Journal of Biological Chemistry.

[82]  A. Kazlauskas,et al.  Phospholipase C-γ1 and phosphatidylinositol 3 kinase are the downstream mediators of the PDGF receptor's mitogenic signal , 1993, Cell.

[83]  R. Birge,et al.  SH2 and SH3‐containing adaptor proteins: redundant or independent mediators of intracellular signal transduction , 1996, Genes to cells : devoted to molecular & cellular mechanisms.

[84]  David R. Kaplan,et al.  Regulation of Neuronal Survival by the Serine-Threonine Protein Kinase Akt , 1997, Science.

[85]  T. Blundell,et al.  Topological similarities in TGF-beta 2, PDGF-BB and NGF define a superfamily of polypeptide growth factors. , 1993, Structure.

[86]  E. Rozengurt,et al.  Platelet-derived growth factor modulation of focal adhesion kinase (p125FAK) and paxillin tyrosine phosphorylation in Swiss 3T3 cells. Bell-shaped dose response and cross-talk with bombesin. , 1994, The Journal of biological chemistry.

[87]  C. Cartwright,et al.  Regulation of the Src tyrosine kinase and Syp tyrosine phosphatase by their cellular association. , 1995, Oncogene.

[88]  T. Borg,et al.  Beta 1 integrin-mediated collagen gel contraction is stimulated by PDGF. , 1990, Experimental cell research.

[89]  H. Inui,et al.  Transduction of mitogenic activity of platelet-derived growth factor (PDGF) AB by PDGF-beta receptor without participation of PDGF-alpha receptor in vascular smooth muscle cells. , 1993, The Journal of biological chemistry.

[90]  A. Miyajima,et al.  Formation of STAT5-containing DNA Binding Complexes in Response to Colony-stimulating Factor-1 and Platelet-derived Growth Factor* , 1996, The Journal of Biological Chemistry.

[91]  D. Bar-Sagi,et al.  Induction of membrane ruffling and fluid-phase pinocytosis in quiescent fibroblasts by ras proteins. , 1986, Science.

[92]  B. Barraclough,et al.  PARAQUAT POISONING , 1976, The Lancet.

[93]  T. Wong,et al.  The cytoplasmic tyrosine kinase FER is associated with the catenin-like substrate pp120 and is activated by growth factors , 1995, Molecular and cellular biology.

[94]  Jonathan A. Cooper,et al.  Phosphorylation sites in the PDGF receptor with different specificities for binding GAP and PI3 kinase in vivo. , 1992, The EMBO journal.

[95]  J Downward,et al.  Ras signalling and apoptosis. , 1998, Current opinion in genetics & development.

[96]  T. Pawson,et al.  Requirement of phospholipase C gamma, the tyrosine phosphatase Syp and the adaptor proteins Shc and Nck for PDGF‐induced DNA synthesis: evidence for the existence of Ras‐dependent and Ras‐independent pathways. , 1996, The EMBO journal.

[97]  B. Burgering,et al.  Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction , 1995, Nature.

[98]  G. Ramponi,et al.  PDGF receptor as a specific in vivo target for low M r phosphotyrosine protein phosphatase , 1995, FEBS letters.

[99]  M. Jaye,et al.  Identification of six novel autophosphorylation sites on fibroblast growth factor receptor 1 and elucidation of their importance in receptor activation and signal transduction , 1996, Molecular and cellular biology.

[100]  C. Wernstedt,et al.  Structural Determinants in the Platelet-derived Growth Factor -Receptor Implicated in Modulation of Chemotaxis (*) , 1996, The Journal of Biological Chemistry.

[101]  S. O. Smith,et al.  Identification of amino acids in the transmembrane and juxtamembrane domains of the platelet-derived growth factor receptor required for productive interaction with the bovine papillomavirus E5 protein , 1997, Journal of virology.

[102]  S. Moriya,et al.  EGF or PDGF receptors activate atypical PKClambda through phosphatidylinositol 3‐kinase. , 1996, The EMBO journal.

[103]  J. Xu,et al.  Extracellular matrix alters PDGF regulation of fibroblast integrins , 1996, The Journal of cell biology.

[104]  T. Hunter,et al.  The PDGF receptor phosphorylates Tyr 138 in the c-Src SH3 domain in vivo reducing peptide ligand binding , 1997, Oncogene.

[105]  H. Ueno,et al.  Inhibition of PDGF beta receptor signal transduction by coexpression of a truncated receptor , 1991, Science.

[106]  C. Heldin,et al.  Isoform‐specific induction of actin reorganization by platelet‐derived growth factor suggests that the functionally active receptor is a dimer. , 1989, The EMBO journal.

[107]  A. Kazlauskas,et al.  Identification of a Putative Syp Substrate, the PDGFβ Receptor (*) , 1995, The Journal of Biological Chemistry.

[108]  S. Spiegel,et al.  Sphingosine-1-phosphate as second messenger in cell proliferation induced by PDGF and FCS mitogens , 1993, Nature.

[109]  C. Heldin,et al.  Immunoglobulin-like Domain 4-mediated Receptor-Receptor Interactions Contribute to Platelet-derived Growth Factor-induced Receptor Dimerization* , 1997, The Journal of Biological Chemistry.

[110]  S. Aaronson,et al.  Five PDGF B amino acid substitutions convert PDGF A to a PDGF B-like transforming molecule. , 1992, The Journal of biological chemistry.

[111]  P. Brecher,et al.  Platelet-derived growth factor receptors on macrovascular endothelial cells mediate relaxation via nitric oxide in rat aorta. , 1992, The Journal of clinical investigation.

[112]  N. Langeland,et al.  A monoclonal antibody against PDGF B-chain inhibits PDGF-induced DNA synthesis in C3H fibroblasts and prevents binding of PDGF to its receptor. , 1990, Biochimica et biophysica acta.

[113]  F. McCormick,et al.  Activation of c‐Raf‐1 by Ras and Src through different mechanisms: activation in vivo and in vitro , 1997, The EMBO journal.

[114]  T. Pawson,et al.  Aberrant Ras regulation and reduced p190 tyrosine phosphorylation in cells lacking p120-Gap , 1997, Molecular and cellular biology.

[115]  A. Gazit,et al.  Platelet‐derived growth factor isoforms prevent cell death during starvation of AKR‐2B fibroblasts , 1994, Journal of cellular physiology.

[116]  K. Meier,et al.  Independent effects of platelet-derived growth factor isoforms on mitogen-activated protein kinase activation and mitogenesis in human dermal fibroblasts. , 1994, The Journal of biological chemistry.

[117]  H. Vetter,et al.  The synergistic effect of PDGF-AA and IGF-1 on VSMC proliferation might be explained by the differential activation of their intracellular signaling pathways. , 1996, Experimental cell research.

[118]  E. Krebs,et al.  The MAPK signaling cascade , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[119]  M. Waterfield,et al.  Platelet-derived growth factor elicits cyclic AMP accumulation in swiss 3T3 cells: Role of prostaglandin production , 1983, Cell.

[120]  G. Ramponi,et al.  Inhibition of cellular response to platelet‐derived growth factor by low M r phosphotyrosine protein phosphatase overexpression , 1994, FEBS letters.

[121]  S. Aaronson,et al.  Inhibition of platelet-derived growth factor autocrine growth stimulation by a monoclonal antibody to the human alpha platelet-derived growth factor receptor. , 1993, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[122]  S. Oyama,et al.  Selective inhibition of platelet-derived growth factor (PDGF) receptor autophosphorylation and PDGF-mediated cellular events by a quinoline derivative. , 1997, Experimental cell research.

[123]  A. Boynton,et al.  Rapid disruption of gap junctional communication and phosphorylation of connexin43 by platelet‐derived growth factor in T51B rat liver epithelial cells expressing platelet‐derived growth factor receptor , 1998, Journal of cellular physiology.

[124]  G. Ramponi,et al.  c-Src activates both STAT1 and STAT3 in PDGF-stimulated NIH3T3 cells. , 1997, Biochemical and biophysical research communications.

[125]  J. Darnell.  STATs and gene regulation. , 1997, Science.

[126]  C. Heldin,et al.  Interaction of platelet-derived growth factor with its fibroblast receptor. Demonstration of ligand degradation and receptor modulation. , 1982, The Journal of biological chemistry.

[127]  A. Sachinidis,et al.  The platelet‐derived growth factor isomers, PDGF‐AA, PDGF‐AB and PDGF‐BB, induce contraction of vascular smooth muscle cells by different intracellular mechanisms , 1990, FEBS letters.

[128]  S. Aaronson,et al.  Isolation of a novel receptor cDNA establishes the existence of two PDGF receptor genes. , 1989, Science.

[129]  C. Heldin,et al.  Effect of receptor kinase inactivation on the rate of internalization and degradation of PDGF and the PDGF beta-receptor , 1991, The Journal of cell biology.

[130]  J. Schlessinger,et al.  How receptor tyrosine kinases activate Ras. , 1993, Trends in biochemical sciences.

[131]  J. Gutkind,et al.  PLC-γ activation is required for PDGF-βR-mediated mitogenesis and monocytic differentiation of myeloid progenitor cells , 1997, Oncogene.

[132]  J. Dumanski,et al.  Deregulation of the platelet-derived growth factor β-chain gene via fusion with collagen gene COL1A1 in dermatof ibrosarcoma protuberans and giant-cell fibroblastoma , 1997, Nature Genetics.

[133]  T. Hunter,et al.  Phospholipase C-γ is a substrate for the PDGF and EGF receptor protein-tyrosine kinases in vivo and in vitro , 1989, Cell.

[134]  S. Moriya,et al.  Platelet-derived growth factor activates protein kinase C epsilon through redundant and independent signaling pathways involving phospholipase C gamma or phosphatidylinositol 3-kinase. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[135]  M. Ruggiero,et al.  Tyrosine mutations within the alpha platelet-derived growth factor receptor kinase insert domain abrogate receptor-associated phosphatidylinositol-3 kinase activity without affecting mitogenic or chemotactic signal transduction , 1991, Molecular and cellular biology.

[136]  C. Marshall,et al.  Ras recruits Raf‐1 to the plasma membrane for activation by tyrosine phosphorylation. , 1995, The EMBO journal.

[137]  T. Pawson,et al.  Platelet-derived growth factor increases the in vivo activity of phospholipase C-gamma 1 and phospholipase C-gamma 2 , 1991, Molecular and cellular biology.

[138]  J. Pollard,et al.  Rho, Rac and Cdc42 regulate actin organization and cell adhesion in macrophages. , 1997, Journal of cell science.

[139]  A. Kazlauskas,et al.  Phosphorylation of tyrosine 720 in the platelet-derived growth factor alpha receptor is required for binding of Grb2 and SHP-2 but not for activation of Ras or cell proliferation , 1996, Molecular and cellular biology.

[140]  L. Claesson‐Welsh,et al.  Requirement for Phosphatidylinositol 3′-Kinase Activity in Platelet-derived Growth Factor-stimulated Tyrosine Phosphorylation of p125 Focal Adhesion Kinase and Paxillin (*) , 1996, The Journal of Biological Chemistry.

[141]  C. Heldin,et al.  Membrane ruffling and chemotaxis transduced by the PDGF beta-receptor require the binding site for phosphatidylinositol 3' kinase. , 1994, Oncogene.

[142]  P. Libby,et al.  PDGF-dependent tyrosine phosphorylation stimulates production of novel polyphosphoinositides in intact cells , 1989, Cell.

[143]  M. Pierre,et al.  Inhibition of G1 cyclin expression and G1 cyclin-dependent protein kinases by cAMP in an astrocytic cell line. , 1994, Biochemical and biophysical research communications.

[144]  C. Heldin,et al.  Platelet-derived growth factor (PDGF)-induced actin rearrangement is deregulated in cells expressing a mutant Y778F PDGF β-receptor , 1998 .

[145]  E. Hirsch,et al.  Impaired migration but not differentiation of haematopoietic stem cells in the absence of β1 integrins , 1996, Nature.

[146]  J. Exton,et al.  Activation of the zeta isozyme of protein kinase C by phosphatidylinositol 3,4,5-trisphosphate. , 1993, The Journal of biological chemistry.

[147]  Maria-Amelia Escobedo,et al.  A novel monoclonal antibody dependent on domain 5 of the platelet-derived growth factor beta receptor inhibits ligand binding and receptor activation. , 1993, Growth factors.

[148]  Paul Stroobant,et al.  Platelet-derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus , 1983, Nature.

[149]  M. Scully,et al.  Identification of a cyclic peptide inhibitor of platelet‐derived growth factor–BB receptor‐binding and mitogen‐induced DNA synthesis in human fibroblasts , 1997, FEBS letters.

[150]  Jiahuai Han,et al.  NIK is a new Ste20‐related kinase that binds NCK and MEKK1 and activates the SAPK/JNK cascade via a conserved regulatory domain , 1997, The EMBO journal.

[151]  S. Cook,et al.  Inhibition by cAMP of Ras-dependent activation of Raf. , 1993, Science.

[152]  C. Heldin,et al.  Similar action of platelet‐derived growth factor and epidermal growth factor in the prereplicative phase of human fibroblasts suggests a common intracellular pathway , 1985, Journal of cellular physiology.

[153]  J. Blenis,et al.  Phosphatidylinositol 3-kinase activation is required for insulin stimulation of pp70 S6 kinase, DNA synthesis, and glucose transporter translocation , 1994, Molecular and cellular biology.

[154]  K. Rubin,et al.  Platelet-derived growth factor-BB stimulates synthesis of the integrin alpha 2-subunit in human diploid fibroblasts. , 1994, Experimental cell research.

[155]  T Pawson,et al.  Direct interaction between Shc and the platelet-derived growth factor beta-receptor. , 1994, The Journal of biological chemistry.

[156]  T. Stossel.  On the crawling of animal cells. , 1993, Science.

[157]  Richard G. W. Anderson,et al.  Localization of Platelet-derived Growth Factor-stimulated Phosphorylation Cascade to Caveolae (*) , 1996, The Journal of Biological Chemistry.

[158]  W. V. van Blitterswijk,et al.  Platelet-derived growth factor activation of mitogen-activated protein kinase depends on the sequential activation of phosphatidylcholine-specific phospholipase C, protein kinase C-zeta and Raf-1. , 1997, The Biochemical journal.

[159]  M. Carroll,et al.  CGP 57148, a tyrosine kinase inhibitor, inhibits the growth of cells expressing BCR-ABL, TEL-ABL, and TEL-PDGFR fusion proteins. , 1997, Blood.

[160]  N. Thanki,et al.  Structural Role of Extracellular Domain 1 of α-Platelet-derived Growth Factor (PDGF) Receptor for PDGF-AA and PDGF-BB Binding (*) , 1995, The Journal of Biological Chemistry.

[161]  E. Edelman,et al.  Antisense oligonucleotide inhibition of PDGFR-beta receptor subunit expression directs suppression of intimal thickening. , 1997, Circulation.

[162]  Jonathan A. Cooper,et al.  A new function for a phosphotyrosine phosphatase: linking GRB2-Sos to a receptor tyrosine kinase , 1994, Molecular and cellular biology.

[163]  C. Heldin,et al.  Pool of ligand‐bound platelet‐derived growth factor β‐receptors remain activated and tyrosine phosphorylated after internalization , 1993, Journal of cellular physiology.

[164]  N. Morisaki,et al.  Regulatory effects of platelet-derived growth factor-AA homodimer on migration of vascular smooth muscle cells. , 1992, The Journal of biological chemistry.

[165]  W. Fantl,et al.  Platelet-derived growth factor receptor mediates activation of ras through different signaling pathways in different cell types , 1993, Molecular and cellular biology.

[166]  W. Fantl,et al.  Mutations of the platelet-derived growth factor receptor that cause a loss of ligand-induced conformational change, subtle changes in kinase activity, and impaired ability to stimulate DNA synthesis , 1989, Molecular and cellular biology.

[167]  A. Klippel,et al.  Membrane localization of phosphatidylinositol 3-kinase is sufficient to activate multiple signal-transducing kinase pathways , 1996, Molecular and cellular biology.

[168]  K. Scharffetter-Kochanek,et al.  Induction of beta 1 integrin synthesis by recombinant platelet-derived growth factor (PDGF-AB) correlates with an enhanced migratory response of human dermal fibroblasts to various extracellular matrix proteins. , 1995, Experimental cell research.

[169]  P. Furet,et al.  Modulation of the SH2 Binding Specificity and Kinase Activity of Src by Tyrosine Phosphorylation within Its SH2 Domain (*) , 1996, The Journal of Biological Chemistry.

[170]  T. Fleming,et al.  Role of alpha beta receptor heterodimer formation in beta platelet-derived growth factor (PDGF) receptor activation by PDGF-AB. , 1991, The Journal of biological chemistry.

[171]  A. Toker,et al.  The Lipid Products of Phosphoinositide 3-Kinase Increase Cell Motility through Protein Kinase C* , 1997, The Journal of Biological Chemistry.

[172]  C. Turck,et al.  Tyrosine 508 of the 85-kilodalton subunit of phosphatidylinositol 3-kinase is phosphorylated by the platelet-derived growth factor receptor. , 1994, Biochemistry.

[173]  Todd R. Golub,et al.  Fusion of PDGF receptor β to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation , 1994, Cell.

[174]  C. Heldin,et al.  Negative feedback regulation of human platelets via autocrine activation of the platelet-derived growth factor alpha-receptor. , 1994, The Journal of biological chemistry.

[175]  M. Vignais,et al.  Platelet-derived growth factor induces phosphorylation of multiple JAK family kinases and STAT proteins , 1996, Molecular and cellular biology.

[176]  C. Heldin,et al.  Selective platelet-derived growth factor receptor kinase blockers reverse sis-transformation. , 1994, Cancer research.

[177]  Andrius Kazlauskas,et al.  PDGF- and insulin-dependent pp70S6k activation mediated by phosphatidylinositol-3-OH kinase , 1994, Nature.

[178]  A. Ullrich,et al.  Formation of signal transfer complexes between stem cell and platelet-derived growth factor receptors and SH2 domain proteins in vitro. , 1995, Biochemistry.

[179]  Weiqun Li,et al.  Identification of a Domain within the Carboxyl-terminal Region of the Platelet-derived Growth Factor (PDGF) Receptor That Mediates the High Transforming Activity of PDGF * , 1996, The Journal of Biological Chemistry.

[180]  A. Kazlauskas,et al.  The kinase-inactive PDGF beta-receptor mediates activation of the MAP kinase cascade via the endogenous PDGF alpha-receptor in HepG2 cells. , 1996, Oncogene.

[181]  C. Alpers,et al.  Inhibition of mesangial cell proliferation and matrix expansion in glomerulonephritis in the rat by antibody to platelet-derived growth factor , 1992, The Journal of experimental medicine.

[182]  L. Cantley,et al.  Platelet-derived growth factor-dependent activation of phosphatidylinositol 3-kinase is regulated by receptor binding of SH2-domain-containing proteins which influence Ras activity , 1996, Molecular and cellular biology.

[183]  G. Carpenter,et al.  Increase of the catalytic activity of phospholipase C-gamma 1 by tyrosine phosphorylation. , 1990, Science.

[184]  N O Petersen,et al.  Aggregation of PDGF‐β receptors in human skin fibroblasts: characterization by image correlation spectroscopy (ICS) , 1997, FEBS letters.

[185]  Anita B. Roberts,et al.  Peptide Growth Factors and Their Receptors I , 1990, Springer Study Edition.

[186]  D. Mahadevan,et al.  β PDGFR‐IgG chimera demonstrates that human β PDGFR Ig‐like domains 1 to 3 are sufficient for high affinity PDGF BB binding , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[187]  W. Fantl,et al.  Activation of Na+/H+ exchange by platelet-derived growth factor involves phosphatidylinositol 3'-kinase and phospholipase C gamma. , 1994, The Journal of biological chemistry.

[188]  C. Wernstedt,et al.  A unique autophosphorylation site in the platelet-derived growth factor alpha receptor from a heterodimeric receptor complex. , 1994, European journal of biochemistry.

[189]  C. Heldin,et al.  Activated platelet‐derived growth factor autocrine pathway drives the transformed phenotype of a human glioblastoma cell line , 1994, Journal of cellular physiology.

[190]  P. Dent,et al.  Inhibition of the EGF-activated MAP kinase signaling pathway by adenosine 3',5'-monophosphate. , 1993, Science.

[191]  T. Ouchi,et al.  Downstream of Crk adaptor signaling pathway: activation of Jun kinase by v-Crk through the guanine nucleotide exchange protein C3G. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[192]  David R. Kaplan,et al.  Direct Regulation of the Akt Proto-Oncogene Product by Phosphatidylinositol-3,4-bisphosphate , 1997, Science.

[193]  S. Aizawa,et al.  Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice , 1995, Nature.

[194]  E Ruoslahti,et al.  Integrins and anoikis. , 1997, Current opinion in cell biology.

[195]  W. Pledger,et al.  Cellular response to platelet-derived growth factor (PDGF)-AB after down-regulation of PDGF alpha-receptors. Evidence that functional binding does not require alpha-receptors. , 1991, The Journal of biological chemistry.

[196]  N. Lydon,et al.  Selective inhibition of the platelet-derived growth factor signal transduction pathway by a protein-tyrosine kinase inhibitor of the 2-phenylaminopyrimidine class. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[197]  T. Takenawa,et al.  Phosphatidic acid that accumulates in platelet-derived growth factor-stimulated Balb/c 3T3 cells is a potential mitogenic signal. , 1992, The Journal of biological chemistry.

[198]  T. Barrett,et al.  Regulation of platelet‐derived growth factor receptor expression by cell context overrides regulation by cytokines , 1996, Journal of cellular physiology.

[199]  S. Fukumoto,et al.  The fumagillin analogue TNP-470 inhibits DNA synthesis of vascular smooth muscle cells stimulated by platelet-derived growth factor and insulin-like growth factor-I. Possible involvement of cyclin-dependent kinase 2. , 1996, Circulation research.

[200]  B. Wipf,et al.  Both homodimeric isoforms of PDGF (AA and BB) have mitogenic and chemotactic activity and stimulate phosphoinositol turnover , 1989, Journal of cellular physiology.

[201]  T. Pawson,et al.  SH2 domains recognize specific phosphopeptide sequences , 1993, Cell.

[202]  A. Kazlauskas,et al.  The GTPase-activating protein of Ras suppresses platelet-derived growth factor beta receptor signaling by silencing phospholipase C-gamma 1 , 1995, Molecular and cellular biology.

[203]  J. Pierce,et al.  Stimulation of the platelet-derived growth factor beta receptor signaling pathway activates protein kinase C-delta , 1994, Molecular and cellular biology.

[204]  J. Exton,et al.  Dissociation of tyrosine phosphorylation and activation of phosphoinositide phospholipase C induced by the protein kinase C inhibitor Ro-31-8220 in Swiss 3T3 cells treated with platelet-derived growth factor. , 1997, Biochimica et biophysica acta.

[205]  S. R. Datta,et al.  Akt Phosphorylation of BAD Couples Survival Signals to the Cell-Intrinsic Death Machinery , 1997, Cell.

[206]  C. Benjamin,et al.  Platelet-derived growth factor stimulates growth factor receptor binding protein-2 association with Shc in vascular smooth muscle cells. , 1994, The Journal of biological chemistry.

[207]  E. Krebs,et al.  Insulin-like growth factor-I and platelet-derived growth factor-BB induce directed migration of human arterial smooth muscle cells via signaling pathways that are distinct from those of proliferation. , 1994, The Journal of clinical investigation.

[208]  G. Yancopoulos,et al.  Identification of in vivo brain-derived neurotrophic factor-stimulated autophosphorylation sites on the TrkB receptor tyrosine kinase by site-directed mutagenesis. , 1994, The Journal of biological chemistry.

[209]  E. Rozengurt,et al.  Tyrosine phosphorylation of p130(cas) by bombesin, lysophosphatidic acid, phorbol esters, and platelet-derived growth factor. Signaling pathways and formation of a p130(cas)-Crk complex. , 1997, The Journal of biological chemistry.

[210]  E. Anggard,et al.  Substantial inhibition of neo-intimal response to balloon injury in the rat carotid artery using a combination of antibodies to platelet-derived growth factor-BB and basic fibroblast growth factor. , 1997, Atherosclerosis.

[211]  G. Carpenter,et al.  Platelet-derived growth factor induces rapid and sustained tyrosine phosphorylation of phospholipase C-gamma in quiescent BALB/c 3T3 cells , 1989, Molecular and cellular biology.

[212]  S. Cook,et al.  Multiple sources of sn-1,2-diacylglycerol in platelet-derived-growth-factor-stimulated Swiss 3T3 fibroblasts. Evidence for activation of phosphoinositidase C and phosphatidylcholine-specific phospholipase D. , 1991, The Biochemical journal.

[213]  A. Zilberstein,et al.  A new series of PDGF receptor tyrosine kinase inhibitors: 3-substituted quinoline derivatives. , 1994, Journal of medicinal chemistry.

[214]  Y. Ebina,et al.  Platelet-derived growth factor triggers translocation of the insulin-regulatable glucose transporter (type 4) predominantly through phosphatidylinositol 3-kinase binding sites on the receptor. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[215]  S. Shen,et al.  Localization and down-regulating role of the protein tyrosine phosphatase PTP2C in membrane ruffles of PDGF-stimulated cells. , 1996, Experimental cell research.

[216]  L. Wang,et al.  Expression of an ATP binding mutant of PKC-delta inhibits Sis-induced transformation of NIH3T3 cells. , 1996, Oncogene.

[217]  Anne J. Ridley,et al.  The small GTP-binding protein rac regulates growth factor-induced membrane ruffling , 1992, Cell.

[218]  B Swolin,et al.  Mice deficient for PDGF B show renal, cardiovascular, and hematological abnormalities. , 1994, Genes & development.

[219]  H. Ohnishi,et al.  Evidence for "response to injury" hypothesis. , 1982, Life sciences.

[220]  J. Taylor‐Papadimitriou,et al.  Production of PDGF‐like growth factor by breast cancer cell lines , 1985, International journal of cancer.

[221]  A. Toker,et al.  Activation of protein kinase C family members by the novel polyphosphoinositides PtdIns-3,4-P2 and PtdIns-3,4,5-P3. , 1994, The Journal of biological chemistry.

[222]  C. Whiteford,et al.  Platelet-derived Growth Factor-dependent Cellular Transformation Requires Either Phospholipase Cγ or Phosphatidylinositol 3 Kinase* , 1997, The Journal of Biological Chemistry.

[223]  A. van Koppen,et al.  PDGF-AB requires PDGF receptor alpha-subunits for high-affinity, but not for low-affinity, binding and signal transduction. , 1993, The Journal of biological chemistry.

[224]  A. D. de Vos,et al.  Vascular endothelial growth factor: crystal structure and functional mapping of the kinase domain receptor binding site. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[225]  G. Mcmahon,et al.  Tyrphostins. 5. Potent inhibitors of platelet-derived growth factor receptor tyrosine kinase: structure-activity relationships in quinoxalines, quinolines, and indole tyrphostins. , 1996, Journal of medicinal chemistry.

[226]  K. Funa,et al.  Characterization of platelet-derived growth factor (PDGF) action on a mouse neuroblastoma cell line, NB41, by introduction of an antisense PDGF beta-receptor RNA. , 1997, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[227]  S. Böhmer,et al.  Activation of platelet‐derived growth factor (PDGF) receptor dephosphorylation in intact Swiss 3T3 cells by elevators of intracellular Ca2+ and cAMP , 1996, FEBS letters.

[228]  C. Heldin,et al.  Phosphorylation of a 72‐kDa protein in PDGF‐stimulated cells which forms complex with c‐Crk, c‐Fyn and Eps15 , 1997, FEBS letters.

[229]  C. Heldin,et al.  Differential effects of the various isoforms of platelet-derived growth factor on chemotaxis of fibroblasts, monocytes, and granulocytes. , 1990, The Journal of clinical investigation.

[230]  C. Heldin,et al.  Involvement of phosphatidylinositide 3'-kinase and Rac in platelet-derived growth factor-induced actin reorganization and chemotaxis. , 1997, Experimental cell research.

[231]  C. Turck,et al.  Distinct phosphotyrosines on a growth factor receptor bind to specific molecules that mediate different signaling pathways , 1992, Cell.

[232]  C. Heldin,et al.  PDGF alpha-receptor mediated cellular responses are not dependent on Src family kinases in endothelial cells. , 1998, Journal of cell science.

[233]  Sheila M. Thomas,et al.  Association of the Shc and Grb2/Sem5 SH2-containing proteins is implicated in activation of the Ras pathway by tyrosine kinases , 1992, Nature.

[234]  E. Krebs,et al.  Platelet-derived Growth Factor Stimulates Protein Kinase A through a Mitogen-activated Protein Kinase-dependent Pathway in Human Arterial Smooth Muscle Cells (*) , 1996, The Journal of Biological Chemistry.

[235]  Nebojsa Janjic,et al.  Inhibitory DNA ligands to platelet-derived growth factor B-chain. , 1996, Biochemistry.

[236]  G. Evan,et al.  Apoptosis of human vascular smooth muscle cells derived from normal vessels and coronary atherosclerotic plaques. , 1995, The Journal of clinical investigation.

[237]  B. Zetter,et al.  Regulation of chemotaxis by the platelet-derived growth factor receptor-β , 1994, Nature.

[238]  C. Heldin,et al.  Dimerization of B-type platelet-derived growth factor receptors occurs after ligand binding and is closely associated with receptor kinase activation. , 1989, The Journal of biological chemistry.

[239]  L. Phillips,et al.  Platelet-derived growth factor BB for the treatment of chronic pressure ulcers , 1992, The Lancet.

[240]  Michael J. Fry,et al.  Phosphatidylinositol-3-OH kinase direct target of Ras , 1994, Nature.

[241]  J. Cooper,et al.  Phosphorylation sites at the C-terminus of the platelet-derived growth factor receptor bind phospholipase C gamma 1. , 1993, Molecular biology of the cell.

[242]  Philippe Soriano.  The PDGF alpha receptor is required for neural crest cell development and for normal patterning of the somites. , 1997, Development.

[243]  M. Liscovitch,et al.  Phospholipase D activation by the mitogens platelet‐derived growth factor and 12‐O‐tetradecanoylphorbol 13‐acetate in NIH‐3T3 cells , 1989, FEBS letters.

[244]  A. Kazlauskas,et al.  The PDGF receptor alpha subunit activates p21ras and triggers DNA synthesis without interacting with rasGAP. , 1994, Oncogene.

[245]  C. Heldin,et al.  PDGF alpha‐ and beta‐receptors activate unique and common signal transduction pathways. , 1992, The EMBO journal.

[246]  J. Backer,et al.  Specific activation of p85-p110 phosphatidylinositol 3'-kinase stimulates DNA synthesis by ras- and p70 S6 kinase-dependent pathways , 1997, Molecular and cellular biology.

[247]  A. Ullrich,et al.  Multiple in vivo phosphorylated tyrosine phosphatase SHP-2 engages binding to Grb2 via tyrosine 584. , 1996, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[248]  K. Malarkey,et al.  Cyclic AMP inhibitors inhibits PDGF-stimulated mitogen-activated protein kinase activity in rat aortic smooth muscle cells via inactivation of c-Raf-1 kinase and induction of MAP kinase phosphatase-1. , 1997, Cellular signalling.

[249]  S. Sebti,et al.  Platelet-derived Growth Factor Receptor Tyrosine Phosphorylation Requires Protein Geranylgeranylation but not Farnesylation* , 1996, The Journal of Biological Chemistry.

[250]  R. Ross.  The pathogenesis of atherosclerosis: a perspective for the 1990s , 1993, Nature.

[251]  R. Pepperkok,et al.  The Src family tyrosine kinases are required for platelet-derived growth factor-mediated signal transduction in NIH 3T3 cells. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[252]  E. Lakatta,et al.  PDGF receptor-to-nucleus signaling of p91 (STAT1 alpha) transcription factor in rat smooth muscle cells. , 1996, Experimental cell research.

[253]  C. Walsh,et al.  Protein-tyrosine-phosphatase SHPTP2 couples platelet-derived growth factor receptor beta to Ras. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[254]  L. Claesson-Welsh,et al.  Platelet-derived growth factor receptor signals. , 1994, The Journal of biological chemistry.

[255]  W. Pledger,et al.  Detergent solubility defines an alternative itinerary for a subpopulation of PDGF β receptors , 1996, Journal of cellular physiology.

[256]  B. Herman,et al.  Platelet-derived growth factor (PDGF) α receptor activation modulates the calcium mobilizing activity of the PDGF β receptor in Balb/c3T3 fibroblasts , 1992 .

[257]  C. Betsholtz,et al.  PDGF-A Signaling Is a Critical Event in Lung Alveolar Myofibroblast Development and Alveogenesis , 1996, Cell.

[258]  K. Rubin,et al.  Stimulation of beta1 integrins on fibroblasts induces PDGF independent tyrosine phosphorylation of PDGF beta-receptors , 1996, The Journal of cell biology.

[259]  F. G. Sauer,et al.  An Antibody Reactive with Domain 4 of the Platelet-derived Growth Factor β Receptor Allows BB Binding while Inhibiting Proliferation by Impairing Receptor Dimerization* , 1997, The Journal of Biological Chemistry.

[260]  A. Fatatis,et al.  Platelet-derived Growth Factor (PDGF)-induced Ca2+ Signaling in the CG4 Oligodendroglial Cell Line and in Transformed Oligodendrocytes Expressing the β-PDGF Receptor* , 1997, The Journal of Biological Chemistry.

[261]  U. Hellman,et al.  Assignment of interchain disulfide bonds in platelet-derived growth factor (PDGF) and evidence for agonist activity of monomeric PDGF. , 1992, The Journal of biological chemistry.

[262]  T. Pawson,et al.  The 64-kDa protein that associates with the platelet-derived growth factor receptor beta subunit via Tyr-1009 is the SH2-containing phosphotyrosine phosphatase Syp. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[263]  G. Evan,et al.  Suppression of c-Myc-induced apoptosis by Ras signalling through PI(3)K and PKB , 1997, Nature.

[264]  E. Rozengurt,et al.  Preferential inhibition of platelet-derived growth factor-stimulated DNA synthesis and protein tyrosine phosphorylation by nordihydroguaiaretic acid. , 1994, The Journal of biological chemistry.

[265]  E. Ruoslahti,et al.  αvβ3 integrin associates with activated insulin and PDGFβ receptors and potentiates the biological activity of PDGF , 1997 .

[266]  H. Abboud,et al.  PDGF stimulates tyrosine phosphorylation of JAK 1 protein tyrosine kinase in human mesangial cells. , 1996, Kidney international.

[267]  K. Takehara,et al.  Differential chemotactic responses mediated by platelet-derived growth factor alpha- and beta-receptors. , 1995, Archives of biochemistry and biophysics.

[268]  F. Grant,et al.  Platelet-derived growth factor (PDGF) stimulates PDGF receptor subunit dimerization and intersubunit trans-phosphorylation. , 1991, The Journal of biological chemistry.

[269]  S. Shamah,et al.  Dominant-negative mutants of platelet-derived growth factor revert the transformed phenotype of human astrocytoma cells , 1993, Molecular and cellular biology.

[270]  S. Shamah,et al.  Dominant-negative mutants of a platelet-derived growth factor gene. , 1990, Genes & development.

[271]  R. Alexander,et al.  Vasoconstriction: a new activity for platelet-derived growth factor. , 1986, Science.

[272]  D. A. Foster,et al.  v-Src activates a unique phospholipase D activity that can be distinguished from the phospholipase D activity activated by phorbol esters. , 1993, The Biochemical journal.

[273]  C. Ellis,et al.  Fibroblast growth factor-2 potentiates vascular smooth muscle cell migration to platelet-derived growth factor: upregulation of alpha2beta1 integrin and disassembly of actin filaments. , 1997, Circulation research.

[274]  S. Courtneidge,et al.  Src family protein tyrosine kinases and cellular signal transduction pathways. , 1995, Current opinion in cell biology.

[275]  P. Kanakaraj,et al.  Ligand-induced interaction between alpha- and beta-type platelet-derived growth factor (PDGF) receptors: role of receptor heterodimers in kinase activation. , 1991, Biochemistry.

[276]  L. Heasley,et al.  Mitogen-activated protein kinase activation is insufficient for growth factor receptor-mediated PC12 cell differentiation , 1995, Molecular and cellular biology.

[277]  L. Fretto,et al.  Mechanism of platelet-derived growth factor (PDGF) AA, AB, and BB binding to alpha and beta PDGF receptor. , 1993, Journal of Biological Chemistry.

[278]  P. Warne,et al.  Role of Phosphoinositide 3-OH Kinase in Cell Transformation and Control of the Actin Cytoskeleton by Ras , 1997, Cell.

[279]  M. Schwartz,et al.  Adhesion to fibronectin stimulates inositol lipid synthesis and enhances PDGF-induced inositol lipid breakdown , 1993, The Journal of cell biology.

[280]  B. Margolis,et al.  Phosphatidylinositol 3′‐kinase is activated by association with IRS‐1 during insulin stimulation. , 1992, The EMBO journal.

[281]  M. Bryckaert,et al.  Collagen-induced binding to human platelets of platelet-derived growth factor leading to inhibition of P43 and P20 phosphorylation. , 1989, The Journal of biological chemistry.

[282]  I. Fishbein,et al.  PDGF-receptor tyrosine kinase blocker AG1295 selectively attenuates smooth muscle cell growth in vitro and reduces neointimal formation after balloon angioplasty in swine. , 1998, Circulation.

[283]  J. Gutkind,et al.  Requirement of phosphatidylinositol-3 kinase for activation of JNK/SAPKs by PDGF. , 1997, Biochemical and biophysical research communications.

[284]  J. Guan,et al.  Stimulation of cell migration by overexpression of focal adhesion kinase and its association with Src and Fyn. , 1996, Journal of cell science.

[285]  F. McCormick,et al.  Regulation of Epidermal Growth Factor Receptor Signaling by Phosphorylation of the Ras Exchange Factor hSOS1 (*) , 1996, The Journal of Biological Chemistry.

[286]  A. N. Meyer,et al.  Cellular transformation by a transmembrane peptide: structural requirements for the bovine papillomavirus E5 oncoprotein. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[287]  T. Matsui,et al.  Chimeric alpha- and beta-platelet-derived growth factor (PDGF) receptors define three immunoglobulin-like domains of the alpha-PDGF receptor that determine PDGF-AA binding specificity. , 1990, The Journal of biological chemistry.

[288]  L. Naldini,et al.  The tyrosine kinase encoded by the MET proto-oncogene is activated by autophosphorylation , 1991, Molecular and cellular biology.

[289]  Elizabeth Yang,et al.  Serine Phosphorylation of Death Agonist BAD in Response to Survival Factor Results in Binding to 14-3-3 Not BCL-XL , 1996, Cell.

[290]  Philippe Soriano,et al.  Abnormal kidney development and hematological disorders in PDGF beta-receptor mutant mice. , 1994, Genes & development.

[291]  H. Band,et al.  Phosphotyrosine binding domain-dependent upregulation of the platelet-derived growth factor receptor alpha signaling cascade by transforming mutants of Cbl: implications for Cbl's function and oncogenicity , 1997, Molecular and cellular biology.

[292]  G. Carpenter,et al.  Phospholipase C-gamma1: regulation of enzyme function and role in growth factor-dependent signal transduction. , 1997, Cytokine & growth factor reviews.

[293]  R. Assoian,et al.  Anchorage-dependent Cell Cycle Progression , 1997, The Journal of cell biology.

[294]  C. Heldin,et al.  Identification of two juxtamembrane autophosphorylation sites in the PDGF beta‐receptor; involvement in the interaction with Src family tyrosine kinases. , 1993, The EMBO journal.

[295]  C. Heldin,et al.  Assignment of intrachain disulfide bonds in platelet-derived growth factor B-chain. , 1993, The Journal of biological chemistry.

[296]  J. Bonner,et al.  Maximal PDGF-induced lung fibroblast chemotaxis requires PDGF receptor-alpha. , 1996, The American journal of physiology.

[297]  H. Davis,et al.  Inhibition of PDGF receptor binding and PDGF-stimulated biological activity in vitro and of intimal lesion formation in vivo by 2-bromomethyl-5-chlorobenzene sulfonylphthalimide. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[298]  J. Bos,et al.  cAMP antagonizes p21ras‐directed activation of extracellular signal‐regulated kinase 2 and phosphorylation of mSos nucleotide exchange factor. , 1993, The EMBO journal.

[299]  C. Heldin,et al.  Neomycin is a platelet-derived growth factor (PDGF) antagonist that allows discrimination of PDGF alpha- and beta-receptor signals in cells expressing both receptor types. , 1992, The Journal of biological chemistry.

[300]  Michael F. Moran,et al.  Requirement for Phospholipase C-γ1 Enzymatic Activity in Growth Factor-Induced Mitogenesis , 1998, Molecular and Cellular Biology.

[301]  G. Carpenter,et al.  Tyrosine residues in bovine phospholipase C-gamma phosphorylated by the epidermal growth factor receptor in vitro. , 1990, The Journal of biological chemistry.

[302]  M. Barone,et al.  Myc but not Fos rescue of PDGF signalling block caused by kinase-inactive Src , 1995, Nature.

[303]  D. Bowen-Pope,et al.  Differential regulation of expression of two platelet-derived growth factor receptor subunits by transforming growth factor-beta. , 1989, The Journal of biological chemistry.

[304]  Lena Claesson-Welsh,et al.  Activation of Stat5 by platelet-derived growth factor (PDGF) is dependent on phosphorylation sites in PDGF β-receptor juxtamembrane and kinase insert domains , 1998, Oncogene.

[305]  C. Heldin,et al.  Ligand-induced ubiquitination of the platelet-derived growth factor beta-receptor plays a negative regulatory role in its mitogenic signaling. , 1993, The Journal of biological chemistry.

[306]  W. Fantl,et al.  Ras-dependent induction of cellular responses by constitutively active phosphatidylinositol-3 kinase. , 1995, Science.

[307]  C. Heldin,et al.  cDNA cloning and expression of the human A-type platelet-derived growth factor (PDGF) receptor establishes structural similarity to the B-type PDGF receptor. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[308]  A. H. Drummond,et al.  Two PDGF‐B chain residues, arginine 27 and isoleucine 30, mediate receptor binding and activation. , 1991, The EMBO journal.

[309]  A. Kazlauskas,et al.  A Role for Src in Signal Relay by the Platelet-derived Growth Factor α Receptor* , 1998, The Journal of Biological Chemistry.

[310]  J. Pierce,et al.  Structural coincidence of alpha PDGFR epitopes binding to platelet-derived growth factor-AA and a potent neutralizing monoclonal antibody. , 1994, The Journal of biological chemistry.

[311]  Jonathan A. Cooper,et al.  Two signaling molecules share a phosphotyrosine-containing binding site in the platelet-derived growth factor receptor , 1993, Molecular and cellular biology.

[312]  H. Vetter,et al.  Gangliosides GM1, GM2 and GM3 inhibit the platelet-derived growth factor-induced signalling transduction pathway in vascular smooth muscle cells by different mechanisms. , 1996, European journal of cell biology.

[313]  S. Lo,et al.  Platelet-derived Growth Factor-induced Formation of Tensin and Phosphoinositide 3-Kinase Complexes* , 1996, The Journal of Biological Chemistry.

[314]  G. Schmid,et al.  Dimerization of extracellular domains of platelet-derived growth factor receptors. A revised model of receptor-ligand interaction. , 1993, The Journal of biological chemistry.

[315]  Weiqun Li,et al.  Differential Requirement of a Motif within the Carboxyl-terminal Domain of α-Platelet-derived Growth Factor (αPDGF) Receptor for PDGF Focus Forming Activity Chemotaxis, or Growth (*) , 1995, The Journal of Biological Chemistry.

[316]  K. Clauser,et al.  Dimerization of the extracellular domain of the human growth hormone receptor by a single hormone molecule. , 1991, Science.

[317]  S. Rhee,et al.  Phospholipase C gamma complexes with ligand-activated platelet-derived growth factor receptors. An intermediate implicated in phospholipase activation. , 1991, The Journal of biological chemistry.

[318]  U. Hellman,et al.  Demonstration of Functionally Different Interactions between Phospholipase C-γ and the Two Types of Platelet-derived Growth Factor Receptors (*) , 1995, The Journal of Biological Chemistry.

[319]  M. Ultsch,et al.  Human growth hormone and extracellular domain of its receptor: crystal structure of the complex. , 1992, Science.

[320]  G. Carpenter,et al.  The regulation of phospholipase C-gamma 1 by phosphatidic acid. Assessment of kinetic parameters. , 1993, The Journal of biological chemistry.

[321]  C. Marshall,et al.  Differential Regulation of Raf-1, A-Raf, and B-Raf by Oncogenic Ras and Tyrosine Kinases* , 1997, The Journal of Biological Chemistry.

[322]  C. Whiteford,et al.  D-3 phosphoinositide metabolism in cells treated with platelet-derived growth factor. , 1996, The Biochemical journal.

[323]  F. McCormick,et al.  An essential role for Rac in Ras transformation , 1995, Nature.

[324]  D. W. Fry,et al.  Inhibitors of tyrosine kinase , 1997, Current opinion in oncology.

[325]  Jonathan A. Cooper,et al.  GTPase-activating protein and phosphatidylinositol 3-kinase bind to distinct regions of the platelet-derived growth factor receptor beta subunit , 1992, Molecular and cellular biology.

[326]  G. Carpenter,et al.  Essential role of the tyrosine kinase substrate phospholipase C-gamma1 in mammalian growth and development. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[327]  C. Walsh,et al.  Potent Stimulation of SH-PTP2 Phosphatase Activity by Simultaneous Occupancy of Both SH2 Domains (*) , 1995, The Journal of Biological Chemistry.

[328]  J. Pouysségur,et al.  The Phosphotyrosine Phosphatase PTP1D, but not PTP1C, Is an Essential Mediator of Fibroblast Proliferation Induced by Tyrosine Kinase and G Protein-coupled Receptors (*) , 1995, The Journal of Biological Chemistry.

[329]  C. Heldin,et al.  Involvement of loop 2 of platelet-derived growth factor-AA and -BB in receptor binding. , 1995, Growth factors.

[330]  G. Cooper,et al.  Requirement for phosphatidylinositol-3 kinase in the prevention of apoptosis by nerve growth factor. , 1995, Science.

[331]  C. Wernstedt,et al.  Mutation of a Src phosphorylation site in the PDGF beta‐receptor leads to increased PDGF‐stimulated chemotaxis but decreased mitogenesis. , 1996, The EMBO journal.

[332]  A. Ullrich,et al.  Structure of the receptor for platelet-derived growth factor helps define a family of closely related growth factor receptors , 1986, Nature.

[333]  M. Shibuya,et al.  Tyrosine phosphorylation sites at amino acids 239 and 240 of Shc are involved in epidermal growth factor-induced mitogenic signaling that is distinct from Ras/mitogen-activated protein kinase activation , 1997, Molecular and cellular biology.

[334]  Andrius Kazlauskas,et al.  The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase , 1995, Cell.

[335]  M. Jaumann,et al.  Identification of individual amino acids in platelet‐derived growth factor that contribute to the specificity towards the β‐type receptor , 1992, FEBS letters.

[336]  M. Eisenstein,et al.  The fourth immunoglobulin domain of the stem cell factor receptor couples ligand binding to signal transduction , 1995, Cell.

[337]  B. Zetter,et al.  The chemotactic response to PDGF-BB: evidence of a role for Ras , 1995, Journal of Cell Biology.

[338]  S. Ōmura,et al.  Degradation Process of Ligand-stimulated Platelet-derived Growth Factor β -Receptor Involves Ubiquitin-Proteasome Proteolytic Pathway * , 1995, The Journal of Biological Chemistry.

[339]  U. Hellman,et al.  Identification of three amino acids in the platelet-derived growth factor (PDGF) B-chain that are important for binding to the PDGF beta-receptor. , 1991, The Journal of biological chemistry.

[340]  A. Kazlauskas,et al.  Tyrosines 1021 and 1009 are phosphorylation sites in the carboxy terminus of the platelet-derived growth factor receptor beta subunit and are required for binding of phospholipase C gamma and a 64-kilodalton protein, respectively , 1993, Molecular and cellular biology.

[341]  N. Tanaka,et al.  STAM, signal transducing adaptor molecule, is associated with Janus kinases and involved in signaling for cell growth and c-myc induction. , 1997, Immunity.

[342]  A. Levitzki,et al.  Tyrosine kinase inhibition: an approach to drug development. , 1995, Science.

[343]  M. Hosang,et al.  Production of platelet-derived growth factor receptor (PDGFR-beta) in E. coli. Mapping ligand binding domain. , 1994, FEBS letters.

[344]  F. McCormick,et al.  Cdc42 regulates anchorage-independent growth and is necessary for Ras transformation , 1997, Molecular and cellular biology.

[345]  Yasushi Saito,et al.  Identification of Tyr-762 in the platelet-derived growth factor α-receptor as the binding site for Crk proteins , 1998, Oncogene.

[346]  J. Blenis,et al.  Activation of pp70/85 S6 kinases in interleukin-2-responsive lymphoid cells is mediated by phosphatidylinositol 3-kinase and inhibited by cyclic AMP , 1995, Molecular and cellular biology.

[347]  Joseph Schlessinger,et al.  Structure of the FGF Receptor Tyrosine Kinase Domain Reveals a Novel Autoinhibitory Mechanism , 1996, Cell.

[348]  V. Ramakrishnan,et al.  Functional Importance of Platelet-derived Growth Factor (PDGF) Receptor Extracellular Immunoglobulin-like Domains , 1997, The Journal of Biological Chemistry.

[349]  C. Marshall,et al.  Specificity of receptor tyrosine kinase signaling: Transient versus sustained extracellular signal-regulated kinase activation , 1995, Cell.

[350]  C. Chang,et al.  Platelet-derived growth factor is an autocrine stimulator for the growth and survival of human esophageal carcinoma cell lines. , 1996, Experimental Cell Research.

[351]  P. Pantazis,et al.  Integration of proviral DNA into the PDGF β-receptor gene in HTLV-I-infected T-cells results in a novel tyrosine kinase product with transforming activity , 1997, Oncogene.

[352]  P. Hawkins,et al.  PDGF stimulates an increase in GTP–Rac via activation of phosphoinositide 3-kinase , 1995, Current Biology.

[353]  C. Heldin,et al.  Tyr-716 in the platelet-derived growth factor beta-receptor kinase insert is involved in GRB2 binding and Ras activation , 1994, Molecular and cellular biology.

[354]  C. Heldin,et al.  INDUCTION OF B-TYPE RECEPTORS FOR PLATELET-DERIVED GROWTH FACTOR IN VASCULAR INFLAMMATION: POSSIBLE IMPLICATIONS FOR DEVELOPMENT OF VASCULAR PROLIFERATIVE LESIONS , 1988, The Lancet.

[355]  C. Heldin,et al.  Localization of platelet-derived growth factor (PDGF) in CHO cells transfected with PDGF A- or B-chain cDNA: retention of PDGF-BB in the endoplasmic reticulum and Golgi complex. , 1990, Journal of cell science.

[356]  A. Kazlauskas,et al.  Disruption of PDGF receptor trafficking by mutation of its PI-3 kinase binding sites. , 1994, Science.

[357]  J. Bishop,et al.  β PDGF receptor mutants defective for mitogenesis promote neurite outgrowth in PC12 cells , 1995, Current Biology.

[358]  C. Heldin,et al.  Ligand-induced polyubiquitination of the platelet-derived growth factor beta-receptor. , 1992, The Journal of biological chemistry.

[359]  R. Stanton,et al.  Signal transduction proteins that associate with the platelet-derived growth factor (PDGF) receptor mediate the PDGF-induced release of glucose-6-phosphate dehydrogenase from permeabilized cells. , 1994, The Journal of biological chemistry.

[360]  A. Ashworth,et al.  An essential role for Rho, Rac, and Cdc42 GTPases in cell cycle progression through G1 , 1995, Science.

[361]  C. Heldin,et al.  Induction of platelet-derived growth factor receptor expression in smooth muscle cells and fibroblasts upon tissue culturing , 1988, The Journal of cell biology.

[362]  S. Aaronson,et al.  A deletion in the extracellular domain of the alpha platelet-derived growth factor (PDGF) receptor differentially impairs PDGF-AA and PDGF-BB binding affinities. , 1992, The Journal of biological chemistry.

[363]  M. Lavin,et al.  Platelet-derived growth factor receptors form a high affinity state in membrane preparations. Kinetics and affinity cross-linking studies. , 1984, The Journal of biological chemistry.

[364]  G. Freund,et al.  Expression of a transmembrane phosphotyrosine phosphatase inhibits cellular response to platelet-derived growth factor and insulin-like growth factor-1. , 1992, The Journal of biological chemistry.

[365]  E. Fleck,et al.  Mitogen-activated protein kinase activation is involved in platelet-derived growth factor-directed migration by vascular smooth muscle cells. , 1997, Hypertension.

[366]  E. Kremmer,et al.  Mapping of the Sites for Ligand Binding and Receptor Dimerization at the Extracellular Domain of the Vascular Endothelial Growth Factor Receptor FLT-1* , 1997, The Journal of Biological Chemistry.