The MIG-2/Integrin Interaction Strengthens Cell-Matrix Adhesion and Modulates Cell Motility*

Integrin-mediated cell-matrix adhesion plays an important role in control of cell behavior. We report here that MIG-2, a widely expressed focal adhesion protein, interacts with β1 and β3 integrin cytoplasmic domains. Integrin binding is mediated by a single site within the MIG-2 FERM domain. Functionally, the MIG-2/integrin interaction recruits MIG-2 to focal adhesions. Furthermore, using αIIbβ3 integrin-expressing Chinese hamster ovary cells, a well described model system for integrin activation, we show that MIG-2 promotes integrin activation and enhances cell-extracellular matrix adhesion. Although MIG-2 is expressed in many cell types, it is deficient in certain colon cancer cells. Expression of MIG-2, but not of an integrin binding-defective MIG-2 mutant, in MIG-2-null colon cancer cells strengthened cell-matrix adhesion, promoted focal adhesion formation, and reduced cell motility. These results suggest that the MIG-2/integrin interaction is an important element in the cellular control of integrin-mediated cell-matrix adhesion and that loss of this interaction likely contributes to high motility of colon cancer cells.

[1]  R. Liddington,et al.  Structural Basis of Integrin Activation by Talin , 2007, Cell.

[2]  V. Gkretsi,et al.  Migfilin Interacts with Vasodilator-stimulated Phosphoprotein (VASP) and Regulates VASP Localization to Cell-Matrix Adhesions and Migration* , 2006, Journal of Biological Chemistry.

[3]  J. Qin,et al.  Regulation of integrin αIIbβ3 activation by distinct regions of its cytoplasmic tails , 2006 .

[4]  D. Critchley,et al.  Genetic, biochemical and structural approaches to talin function. , 2005, Biochemical Society transactions.

[5]  Chuanyue Wu.  PINCH, N(i)ck and the ILK: network wiring at cell-matrix adhesions. , 2005, Trends in cell biology.

[6]  Chuanyue Wu.  Migfilin and its binding partners: from cell biology to human diseases , 2005, Journal of Cell Science.

[7]  Simon C Watkins,et al.  Physical and functional association of migfilin with cell-cell adhesions , 2005, Journal of Cell Science.

[8]  I. Campbell,et al.  The talin-tail interaction places integrin activation on FERM ground. , 2004, Trends in biochemical sciences.

[9]  O. Vinogradova,et al.  Integrin Bidirectional Signaling: A Molecular View , 2004, PLoS biology.

[10]  J. Qin,et al.  Membrane-mediated structural transitions at the cytoplasmic face during integrin activation , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[11]  M. Beckerle,et al.  The Kindler Syndrome Protein Is Regulated by Transforming Growth Factor-β and Involved in Integrin-mediated Adhesion* , 2004, Journal of Biological Chemistry.

[12]  D. Webb,et al.  Talin: an emerging focal point of adhesion dynamics. , 2004, Current opinion in cell biology.

[13]  Tomohiko Fukuda,et al.  PINCH-1 Is an Obligate Partner of Integrin-linked Kinase (ILK) Functioning in Cell Shape Modulation, Motility, and Survival* , 2003, Journal of Biological Chemistry.

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

[15]  Minsoo Kim,et al.  Bidirectional Transmembrane Signaling by Cytoplasmic Domain Separation in Integrins , 2003, Science.

[16]  Manuel C. Peitsch,et al.  SWISS-MODEL: an automated protein homology-modeling server , 2003, Nucleic Acids Res..

[17]  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.

[18]  Richard O Hynes,et al.  Integrins Bidirectional, Allosteric Signaling Machines , 2002, Cell.

[19]  Jun Qin,et al.  A Structural Mechanism of Integrin αIIbβ3 “Inside-Out” Activation as Regulated by Its Cytoplasmic Face , 2002, Cell.

[20]  Lida Guo,et al.  Regulation of fibronectin matrix deposition and cell proliferation by the PINCH‐ILK‐CH‐ILKBP complex , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[21]  David A. Calderwood,et al.  The Phosphotyrosine Binding-like Domain of Talin Activates Integrins* , 2002, The Journal of Biological Chemistry.

[22]  D. Moerman,et al.  C. elegans PAT-4/ILK Functions as an Adaptor Protein within Integrin Adhesion Complexes , 2002, Current Biology.

[23]  Lida Guo,et al.  A Critical Role of the PINCH-Integrin-linked Kinase Interaction in the Regulation of Cell Shape Change and Migration* , 2002, The Journal of Biological Chemistry.

[24]  Kenneth M. Yamada,et al.  Transmembrane crosstalk between the extracellular matrix and the cytoskeleton , 2001, Nature Reviews Molecular Cell Biology.

[25]  J. Welsh,et al.  Molecular classification of human carcinomas by use of gene expression signatures. , 2001, Cancer research.

[26]  M. Ginsberg,et al.  Integrin cytoplasmic domain-binding proteins. , 2000, Journal of cell science.

[27]  David A. Calderwood,et al.  Integrins and Actin Filaments: Reciprocal Regulation of Cell Adhesion and Signaling* , 2000, The Journal of Biological Chemistry.

[28]  D. Moerman,et al.  The UNC-112 Gene in Caenorhabditis elegansEncodes a Novel Component of Cell–Matrix Adhesion Structures Required for Integrin Localization in the Muscle Cell Membrane , 2000, The Journal of cell biology.

[29]  M. Schaller,et al.  UNC112. A new regulator of cell-extracellular matrix adhesions? , 2000, The Journal of cell biology.

[30]  Christian A. Rees,et al.  Systematic variation in gene expression patterns in human cancer cell lines , 2000, Nature Genetics.

[31]  R. Mayne,et al.  A Novel Muscle-Specific β1 Integrin Binding Protein (Mibp) That Modulates Myogenic Differentiation , 1999, The Journal of cell biology.

[32]  R. Hynes,et al.  The Talin Head Domain Binds to Integrin β Subunit Cytoplasmic Tails and Regulates Integrin Activation* , 1999, The Journal of Biological Chemistry.

[33]  G. Lippens,et al.  Divalent Cations Differentially Regulate Integrin αIIb Cytoplasmic Tail Binding to β3 and to Calcium- and Integrin-binding Protein* , 1999, The Journal of Biological Chemistry.

[34]  R J Read,et al.  Crystallography & NMR system: A new software suite for macromolecular structure determination. , 1998, Acta crystallographica. Section D, Biological crystallography.

[35]  R L Juliano,et al.  Integrin signaling and cell growth control. , 1998, Current opinion in cell biology.

[36]  D. Lauffenburger,et al.  Cell Migration: A Physically Integrated Molecular Process , 1996, Cell.

[37]  J. Rosa,et al.  A point mutation in the integrin beta 3 cytoplasmic domain (S752-->P) impairs bidirectional signaling through alpha IIb beta 3 (platelet glycoprotein IIb-IIIa). , 1994, Blood.

[38]  B. Beutler,et al.  Prolonged and effective blockade of tumor necrosis factor activity through adenovirus-mediated gene transfer. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[39]  J. Rosa,et al.  Ser-752-->Pro mutation in the cytoplasmic domain of integrin beta 3 subunit and defective activation of platelet integrin alpha IIb beta 3 (glycoprotein IIb-IIIa) in a variant of Glanzmann thrombasthenia. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[40]  E. Ruoslahti,et al.  Motility of fibronectin receptor-deficient cells on fibronectin and vitronectin: collaborative interactions among integrins [published erratum appears in J Cell Biol 1992 Jul;118(1):217] , 1992, The Journal of cell biology.

[41]  D. McClay,et al.  Cell adhesion to fibronectin and tenascin: quantitative measurements of initial binding and subsequent strengthening response , 1989, The Journal of cell biology.

[42]  M. Beckerle,et al.  Interaction of plasma membrane fibronectin receptor with talin—a transmembrane linkage , 1986, Nature.

[43]  R. Liddington,et al.  Structural determinants of integrin recognition by talin. , 2003, Molecular cell.

[44]  W. Delano.  The PyMOL Molecular Graphics System , 2002 .

[45]  K. Burridge,et al.  Focal adhesions, contractility, and signaling. , 1996, Annual review of cell and developmental biology.

[46]  A. Huttenlocher,et al.  Adhesion in cell migration. , 1995, Current opinion in cell biology.

[47]  M. Schwartz,et al.  Integrins: emerging paradigms of signal transduction. , 1995, Annual review of cell and developmental biology.

[48]  M. Hemler,et al.  The leukocyte 1 integrins , 1995 .