Integrin signaling: specificity and control of cell survival and cell cycle progression.

Integrin-mediated adhesion to the extracellular matrix plays an important role in regulating cell survival and proliferation. There is now increasing evidence that integrins activate shared as well as subgroup-specific signaling pathways. The signals from these adhesion receptors are integrated with those originating from growth factor and cytokine receptors in order to organize the cytoskeleton, stimulate mitogen-activated protein kinase cascades, and regulate immediate early gene expression. The repertoire of integrins and composition of the extracellular matrix appear to dictate whether a cell will survive, proliferate or exit the cell cycle and differentiate in response to soluble factors.

[1]  Dan R. Littman,et al.  Signal transduction by lymphocyte antigen receptors , 1994, Cell.

[2]  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.

[3]  J. Chung,et al.  Thrombspondin Acts via Integrin-associated Protein to Activate the Platelet Integrin αIIbβ3 * , 1997, The Journal of Biological Chemistry.

[4]  L. Chong,et al.  The small GTP-binding protein Rho regulates a phosphatidylinositol 4-phosphate 5-kinase in mammalian cells , 1994, Cell.

[5]  J. Wehland,et al.  Mena, a Relative of VASP and Drosophila Enabled, Is Implicated in the Control of Microfilament Dynamics , 1996, Cell.

[6]  James M. Roberts,et al.  Fibrillar Collagen Inhibits Arterial Smooth Muscle Proliferation through Regulation of Cdk2 Inhibitors , 1996, Cell.

[7]  E. Ruoslahti,et al.  Introduction of p130cas signaling complex formation upon integrin-mediated cell adhesion: a role for Src family kinases , 1996, Molecular and cellular biology.

[8]  J. Brugge,et al.  Phosphatidylinositol 3-kinase is required for integrin-stimulated AKT and Raf-1/mitogen-activated protein kinase pathway activation , 1997, Molecular and cellular biology.

[9]  S. Dedhar,et al.  Regulation of cell adhesion and anchorage-dependent growth by a new β1-integrin-linked protein kinase , 1996, Nature.

[10]  K. Kaibuchi,et al.  Formation of Actin Stress Fibers and Focal Adhesions Enhanced by Rho-Kinase , 1997, Science.

[11]  J. Parsons,et al.  Interaction of Focal Adhesion Kinase with Cytoskeletal Protein Talin (*) , 1995, The Journal of Biological Chemistry.

[12]  S. Dedhar,et al.  Overexpression of the Integrin-linked Kinase Promotes Anchorage-independent Cell Cycle Progression* , 1997, The Journal of Biological Chemistry.

[13]  F. Berditchevski,et al.  A Novel Link between Integrins, Transmembrane-4 Superfamily Proteins (CD63 and CD81), and Phosphatidylinositol 4-Kinase* , 1997, The Journal of Biological Chemistry.

[14]  M. Taggart,et al.  The effects of vascular smooth muscle caldesmon on force production by ‘desensitised’ skeletal muscle fibres , 1988, FEBS letters.

[15]  J. Parsons,et al.  Autophosphorylation of the focal adhesion kinase, pp125FAK, directs SH2-dependent binding of pp60src , 1994, Molecular and cellular biology.

[16]  E. Schwarz,et al.  Molecular cloning of integrin-associated protein: an immunoglobulin family member with multiple membrane-spanning domains implicated in alpha v beta 3-dependent ligand binding , 1993, The Journal of cell biology.

[17]  James M. Roberts,et al.  Adhesion-dependent cell cycle progression linked to the expression of cyclin D1, activation of cyclin E-cdk2, and phosphorylation of the retinoblastoma protein , 1996, The Journal of cell biology.

[18]  A. Hall,et al.  The assembly of integrin adhesion complexes requires both extracellular matrix and intracellular rho/rac GTPases , 1995, The Journal of cell biology.

[19]  C. Hall,et al.  Regulation of Phosphorylation Pathways by p21 GTPases , 1996 .

[20]  M. Zutter,et al.  Characterization of novel complexes on the cell surface between integrins and proteins with 4 transmembrane domains (TM4 proteins). , 1996, Molecular biology of the cell.

[21]  Tony Pawson,et al.  Protein modules and signalling networks , 1995, Nature.

[22]  C H Streuli,et al.  Laminin mediates tissue-specific gene expression in mammary epithelia , 1995, The Journal of cell biology.

[23]  M. Brown,et al.  Identification of LIM3 as the principal determinant of paxillin focal adhesion localization and characterization of a novel motif on paxillin directing vinculin and focal adhesion kinase binding , 1996, The Journal of cell biology.

[24]  J. Parsons,et al.  A mechanism for regulation of the adhesion-associated protein tyrosine kinase pp125FAK , 1996, Nature.

[25]  T. Hunter,et al.  Focal Adhesion Kinase Overexpression Enhances Ras-dependent Integrin Signaling to ERK2/Mitogen-activated Protein Kinase through Interactions with and Activation of c-Src* , 1997, The Journal of Biological Chemistry.

[26]  R. Hynes Targeted mutations in cell adhesion genes: what have we learned from them? , 1996, Developmental biology.

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

[28]  M. Schwartz,et al.  Inhibition of cell cycle progression by the alternatively spliced integrin beta 1C. , 1995, Science.

[29]  E. Ruoslahti,et al.  Control of adhesion-dependent cell survival by focal adhesion kinase , 1996, The Journal of cell biology.

[30]  W. Cance,et al.  Overexpression of the focal adhesion kinase (p125FAK) in invasive human tumors. , 1995, Cancer research.

[31]  Richard O. Hynes,et al.  Integrins: Versatility, modulation, and signaling in cell adhesion , 1992, Cell.

[32]  T. Hunter,et al.  Evidence for in vivo phosphorylation of the Grb2 SH2-domain binding site on focal adhesion kinase by Src-family protein-tyrosine kinases , 1996, Molecular and cellular biology.

[33]  F. Giancotti,et al.  The Adaptor Protein Shc Couples a Class of Integrins to the Control of Cell Cycle Progression , 1996, Cell.

[34]  M. Karin The Regulation of AP-1 Activity by Mitogen-activated Protein Kinases (*) , 1995, The Journal of Biological Chemistry.

[35]  David A. Cheresh,et al.  Regulation of Cell Motility by Mitogen-activated Protein Kinase , 1997, The Journal of cell biology.

[36]  C. Der,et al.  The coupling of α6β4 integrin to Ras–MAP kinase pathways mediated by Shc controls keratinocyte proliferation , 1997 .

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

[38]  J. Schlessinger,et al.  Signal transduction by the α6β4 integrin: distinct β4 subunit sites mediate recruitment of Shc/Grb2 and association with the cytoskeleton of hemidesmosomes , 1995 .

[39]  F M Watt,et al.  Regulation of development and differentiation by the extracellular matrix. , 1993, Development.

[40]  J. Parsons,et al.  Integrin-mediated signalling: regulation by protein tyrosine kinases and small GTP-binding proteins. , 1996, Current opinion in cell biology.

[41]  Kozo Kaibuchi,et al.  Regulation of Myosin Phosphatase by Rho and Rho-Associated Kinase (Rho-Kinase) , 1996, Science.

[42]  K. Burridge,et al.  Rho-stimulated contractility drives the formation of stress fibers and focal adhesions , 1996, The Journal of cell biology.

[43]  T. Hunter,et al.  Fibronectin-stimulated signaling from a focal adhesion kinase-c-Src complex: involvement of the Grb2, p130cas, and Nck adaptor proteins , 1997, Molecular and cellular biology.

[44]  C. S. Chen,et al.  Geometric control of cell life and death. , 1997, Science.

[45]  D. Sheppard,et al.  Identification of a Sequence within the Integrin β6 Subunit Cytoplasmic Domain That Is Required to Support the Specific Effect of αvβ6 on Proliferation in Three-dimensional Culture* , 1996, The Journal of Biological Chemistry.

[46]  Jonathan A. Cooper,et al.  Control of actin assembly at filament ends. , 1995, Annual review of cell and developmental biology.

[47]  M. Schwartz,et al.  Integrin regulation of c-Abl tyrosine kinase activity and cytoplasmic-nuclear transport. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[48]  K. Yamada,et al.  Integrin function: molecular hierarchies of cytoskeletal and signaling molecules , 1995, The Journal of cell biology.

[49]  J. Muschler,et al.  Integrin alpha subunit ratios, cytoplasmic domains, and growth factor synergy regulate muscle proliferation and differentiation , 1996, The Journal of cell biology.

[50]  F. Giancotti,et al.  The β4 subunit cytoplasmic domain mediates the interaction of α6β4 integrin with the cytoskeleton of hemidesmosomes , 1993 .

[51]  J. Parsons,et al.  Focal adhesion kinase and paxillin bind to peptides mimicking beta integrin cytoplasmic domains , 1995, The Journal of cell biology.

[52]  G. Bokoch,et al.  Physical association of the small GTPase Rho with a 68-kDa phosphatidylinositol 4-phosphate 5-kinase in Swiss 3T3 cells. , 1996, Molecular biology of the cell.

[53]  C. Albanese,et al.  Transforming p21ras Mutants and c-Ets-2 Activate the Cyclin D1 Promoter through Distinguishable Regions (*) , 1995, The Journal of Biological Chemistry.

[54]  A. Gilmore,et al.  Regulation of vinculin binding to talin and actin by phosphatidyl-inositol-4-5-bisphosphate , 1996, Nature.

[55]  R. Juliano,et al.  Cell Anchorage Permits Efficient Signal Transduction Between Ras and Its Downstream Kinases* , 1997, The Journal of Biological Chemistry.

[56]  F. Giancotti,et al.  Integrin-mediated adhesion and signaling in tumorigenesis. , 1994, Biochimica et biophysica acta.

[57]  Asim Khwaja,et al.  Matrix adhesion and Ras transformation both activate a phosphoinositide 3‐OH kinase and protein kinase B/Akt cellular survival pathway , 1997, The EMBO journal.

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

[59]  J. Parsons,et al.  Integrin-dependent Activation of the p70 Ribosomal S6 Kinase Signaling Pathway* , 1996, The Journal of Biological Chemistry.

[60]  J. Guan,et al.  Phosphorylation of Tyrosine 397 in Focal Adhesion Kinase Is Required for Binding Phosphatidylinositol 3-Kinase* , 1996, The Journal of Biological Chemistry.

[61]  K. Yamada,et al.  Integrins can collaborate with growth factors for phosphorylation of receptor tyrosine kinases and MAP kinase activation: roles of integrin aggregation and occupancy of receptors , 1996, The Journal of cell biology.

[62]  F. Giancotti Signal transduction by the α6β4 integrin: Charting the path between laminin binding and nuclear events , 1996 .

[63]  L. Romer,et al.  Inhibition of focal adhesion kinase (FAK) signaling in focal adhesions decreases cell motility and proliferation. , 1996, Molecular biology of the cell.

[64]  J. Blenis,et al.  The 70 kDa S6 kinase: regulation of a kinase with multiple roles in mitogenic signalling. , 1995, Current opinion in cell biology.

[65]  C. Watson,et al.  Stat5 as a Target for Regulation by Extracellular Matrix (*) , 1995, The Journal of Biological Chemistry.

[66]  J. Chant,et al.  Rac and Cdc42 Induce Actin Polymerization and G1 Cell Cycle Progression Independently of p65PAK and the JNK/SAPK MAP Kinase Cascade , 1996, Cell.

[67]  T. Hunter,et al.  Dependence of Cyclin E-CDK2 Kinase Activity on Cell Anchorage , 1996, Science.

[68]  A. Aplin,et al.  Integrin-mediated Activation of MAP Kinase Is Independent of FAK: Evidence for Dual Integrin Signaling Pathways in Fibroblasts , 1997, The Journal of cell biology.

[69]  D. Bar-Sagi,et al.  RAC Regulation of Actin Polymerization and Proliferation by a Pathway Distinct from Jun Kinase , 1996, Science.

[70]  R. Hynes,et al.  Ras Activation Is Necessary for Integrin-mediated Activation of Extracellular Signal-regulated Kinase 2 and Cytosolic Phospholipase A2 but Not for Cytoskeletal Organization* , 1996, The Journal of Biological Chemistry.

[71]  H. Kleinman,et al.  Role of laminin and basement membrane in the morphological differentiation of human endothelial cells into capillary-like structures , 1988, The Journal of cell biology.

[72]  M. Schwartz,et al.  Involvement of the Small GTPase Rho in Integrin-mediated Activation of Mitogen-activated Protein Kinase* , 1996, The Journal of Biological Chemistry.

[73]  C. Der,et al.  Integrin-mediated activation of mitogen-activated protein (MAP) or extracellular signal-related kinase kinase (MEK) and kinase is independent of ras , 1996 .