Genetic and cell biological analysis of integrin outside-in signaling.

Integrins are cell surface transmembrane receptors that recognize and bind to extracellular matrix proteins and counter receptors. Binding of activated integrins to their ligands induces a vast number of structural and signaling changes within the cell. Large, multimolecular complexes assemble onto the cytoplasmic tails of activated integrins to engage and organize the cytoskeleton, and activate signaling pathways that ultimately lead to changes in gene expression. Additionally, integrin-mediated signaling intersects with growth factor-mediated signaling through various levels of cross-talk. This review discusses recent work that has tremendously broadened our understanding of the complexity of integrin-mediated signaling.

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[61]  D. Pei,et al.  A chemical approach to the identification of tensin-binding proteins. , 2007, ACS chemical biology.

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[63]  Yoav Freund,et al.  Lamellipodial Actin Mechanically Links Myosin Activity with Adhesion-Site Formation , 2007, Cell.

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[67]  D. Ingber,et al.  α-Actinin-4 Is Required for Normal Podocyte Adhesion* , 2007, Journal of Biological Chemistry.

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[69]  M. Post,et al.  Stretch‐activated signaling pathways responsible for early response gene expression in fetal lung epithelial cells , 2007, Journal of cellular physiology.

[70]  Claire M Brown,et al.  Probing the integrin-actin linkage using high-resolution protein velocity mapping , 2006, Journal of Cell Science.

[71]  Michael P. Sheetz,et al.  Force Sensing by Mechanical Extension of the Src Family Kinase Substrate p130Cas , 2006, Cell.

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[73]  Anna Huttenlocher,et al.  Talin1 Regulates TCR-Mediated LFA-1 Function1 , 2006, The Journal of Immunology.

[74]  J. Settleman,et al.  Integrin signaling through Arg activates p190RhoGAP by promoting its binding to p120RasGAP and recruitment to the membrane. , 2006, Molecular biology of the cell.

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[76]  P. Flevaris,et al.  Tyrosine Phosphorylation of the Integrin β3 Subunit Regulates β3 Cleavage by Calpain* , 2006, Journal of Biological Chemistry.

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[86]  Sami Alom Ruiz,et al.  An inhibitory role for FAK in regulating proliferation: a link between limited adhesion and RhoA-ROCK signaling , 2006, The Journal of cell biology.

[87]  R. Liddington,et al.  Role of vinculin in regulating focal adhesion turnover. , 2006, European journal of cell biology.

[88]  R. O'Connor,et al.  Insulin-Like Growth Factor I Controls a Mutually Exclusive Association of RACK1 with Protein Phosphatase 2A and β1 Integrin To Promote Cell Migration , 2006, Molecular and Cellular Biology.

[89]  G. Tanentzapf,et al.  An interaction between integrin and the talin FERM domain mediates integrin activation but not linkage to the cytoskeleton , 2006, Nature Cell Biology.

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[96]  L. Maile,et al.  Insulin-like growth factor-i signaling in smooth muscle cells is regulated by ligand binding to the 177CYDMKTTC184 sequence of the β3-subunit of αVβ3 , 2006 .

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[98]  M. Messi,et al.  Motor neurone targeting of IGF‐1 prevents specific force decline in ageing mouse muscle , 2006, The Journal of physiology.

[99]  D. Ingber,et al.  α4β1-dependent adhesion strengthening under mechanical strain is regulated by paxillin association with the α4-cytoplasmic domain , 2005, The Journal of cell biology.

[100]  J. Guan,et al.  Inactivation of focal adhesion kinase in cardiomyocytes promotes eccentric cardiac hypertrophy and fibrosis in mice. , 2005, The Journal of clinical investigation.

[101]  S. Fagerholm,et al.  Specific integrin α and β chain phosphorylations regulate LFA-1 activation through affinity-dependent and -independent mechanisms , 2005, The Journal of cell biology.

[102]  Alexandre R Gingras,et al.  Mapping and Consensus Sequence Identification for Multiple Vinculin Binding Sites within the Talin Rod* , 2005, Journal of Biological Chemistry.

[103]  J. Shabanowitz,et al.  FAK phosphorylation sites mapped by mass spectrometry , 2005, Journal of Cell Science.

[104]  J. Shabanowitz,et al.  Talin phosphorylation sites mapped by mass spectrometry , 2005, Journal of Cell Science.

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[106]  Klemens Rottner,et al.  Cdc42 is not essential for filopodium formation, directed migration, cell polarization, and mitosis in fibroblastoid cells. , 2005, Molecular biology of the cell.

[107]  J. Small,et al.  The comings and goings of actin: coupling protrusion and retraction in cell motility. , 2005, Current opinion in cell biology.

[108]  Dean Sheppard,et al.  Integrin-mediated activation of latent transforming growth factor β , 2005, Cancer and Metastasis Reviews.

[109]  S. Dedhar,et al.  Integrin-linked kinase activity regulates Rac- and Cdc42-mediated actin cytoskeleton reorganization via α-PIX , 2005, Oncogene.

[110]  Andrés J. García,et al.  Cell adhesion strengthening: contributions of adhesive area, integrin binding, and focal adhesion assembly. , 2005, Molecular biology of the cell.

[111]  M. Ginsberg,et al.  Specification of the Direction of Adhesive Signaling by the Integrin β Cytoplasmic Domain* , 2005, Journal of Biological Chemistry.

[112]  R. Assoian,et al.  Regulation of growth factor signaling and cell cycle progression by cell adhesion and adhesion-dependent changes in cellular tension. , 2005, Cytokine & growth factor reviews.

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[114]  L. Silengo,et al.  Systematic Analysis of the Epidermal Growth Factor Receptor by Mass Spectrometry Reveals Stimulation-dependent Multisite Phosphorylation*S , 2005, Molecular & Cellular Proteomics.

[115]  Huilin Zhou,et al.  Cell junction-associated proteins IQGAP1, MAGI-2, CASK, spectrins, and alpha-actinin are components of the nephrin multiprotein complex. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[116]  D. Lawrence,et al.  The Role of Protein-tyrosine Phosphatase 1B in Integrin Signaling* , 2005, Journal of Biological Chemistry.

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[118]  E. Schaefer,et al.  β3 Tyrosine Phosphorylation and αvβ3-mediated Adhesion Are Required for Vav1 Association and Rho Activation in Leukocytes* , 2005, Journal of Biological Chemistry.

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[120]  S. Lo,et al.  Inactivation of tensin3 in mice results in growth retardation and postnatal lethality. , 2005, Developmental biology.

[121]  R. O'Connor,et al.  RACK1-mediated Integration of Adhesion and Insulin-like Growth Factor I (IGF-I) Signaling and Cell Migration Are Defective in Cells Expressing an IGF-I Receptor Mutated at Tyrosines 1250 and 1251* , 2005, Journal of Biological Chemistry.

[122]  B. Geiger,et al.  Characterization of a Novel GTPase-activating Protein Associated with Focal Adhesions and the Actin Cytoskeleton* , 2005, Journal of Biological Chemistry.

[123]  J. Qin,et al.  Structure of an ultraweak protein-protein complex and its crucial role in regulation of cell morphology and motility. , 2005, Molecular cell.

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[139]  C. Lautier,et al.  IGF-I receptor mutations resulting in intrauterine and postnatal growth retardation. , 2003, The New England journal of medicine.

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[143]  C. Voermans,et al.  The C-terminal Domain of Rac1 Contains Two Motifs That Control Targeting and Signaling Specificity* , 2003, Journal of Biological Chemistry.

[144]  R. Liddington,et al.  Talin Binding to Integrin ß Tails: A Final Common Step in Integrin Activation , 2003, Science.

[145]  J. Schwarzbauer,et al.  Talin loss-of-function uncovers roles in cell contractility and migration in C. elegans , 2003, Journal of Cell Science.

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[148]  M. Sheetz,et al.  Force‐dependent integrin–cytoskeleton linkage formation requires downregulation of focal complex dynamics by Shp2 , 2003, The EMBO journal.

[149]  K. Anderson,et al.  Insulin-like growth factor-1 induces adhesion and migration in human multiple myeloma cells via activation of beta1-integrin and phosphatidylinositol 3'-kinase/AKT signaling. , 2003, Cancer research.

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[152]  J. Parsons,et al.  PAK1 phosphorylation of MEK1 regulates fibronectin-stimulated MAPK activation , 2003, The Journal of cell biology.

[153]  Michael P. Sheetz,et al.  Two-piconewton slip bond between fibronectin and the cytoskeleton depends on talin , 2003, Nature.

[154]  D. Schlaepfer,et al.  Direct Interaction of Focal Adhesion Kinase with p190RhoGEF* , 2003, Journal of Biological Chemistry.

[155]  J. Qin,et al.  Structural and functional insights into PINCH LIM4 domain–mediated integrin signaling , 2003, Nature Structural Biology.

[156]  R. Gerszten,et al.  Mice deficient in α-actinin-4 have severe glomerular disease , 2003 .

[157]  Kenneth M. Yamada,et al.  Specific β1 Integrin Site Selectively Regulates Akt/Protein Kinase B Signaling via Local Activation of Protein Phosphatase 2A* , 2003, The Journal of Biological Chemistry.

[158]  Michael P. Sheetz,et al.  RPTP-α acts as a transducer of mechanical force on αv/β3-integrin–cytoskeleton linkages , 2003, The Journal of cell biology.

[159]  K. Tachibana,et al.  Signaling between Focal Adhesion Kinase and Trio* , 2003, The Journal of Biological Chemistry.

[160]  Y. Tu,et al.  Migfilin and Mig-2 Link Focal Adhesions to Filamin and the Actin Cytoskeleton and Function in Cell Shape Modulation , 2003, Cell.

[161]  Takao Sakai,et al.  Integrin-linked kinase (ILK) is required for polarizing the epiblast, cell adhesion, and controlling actin accumulation. , 2003, Genes & development.

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[164]  David A Calderwood,et al.  Integrin β cytoplasmic domain interactions with phosphotyrosine-binding domains: A structural prototype for diversity in integrin signaling , 2003, Proceedings of the National Academy of Sciences of the United States of America.

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[170]  L. Maile,et al.  The alphaVbeta3 integrin regulates insulin-like growth factor I (IGF-I) receptor phosphorylation by altering the rate of recruitment of the Src-homology 2-containing phosphotyrosine phosphatase-2 to the activated IGF-I receptor. , 2002, Endocrinology.

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[173]  S. Lo,et al.  Cten, a COOH-terminal tensin-like protein with prostate restricted expression, is down-regulated in prostate cancer. , 2002, Cancer research.

[174]  Charles Boone,et al.  Role of Formins in Actin Assembly: Nucleation and Barbed-End Association , 2002, Science.

[175]  A. Karginov,et al.  The association of ASAP1, an ADP ribosylation factor-GTPase activating protein, with focal adhesion kinase contributes to the process of focal adhesion assembly. , 2002, Molecular biology of the cell.

[176]  J. Parsons,et al.  Integrin connections map: to infinity and beyond. , 2002, Science.

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