Integrin Modulation by Lateral Association

integrin-associated transmembrane protein Chinese hamster ovary conventional protein kinase C phosphatidylinositol 4-kinase focal adhesion kinase protein kinase C phosphatidylinositol 4,5-bisphosphate Integrins are a major family of cell-matrix and cell-cell receptors. Bidirectional signal transmission between the extracellular matrix or other integrin ligands and the submembranous cytoskeleton and associated adaptor proteins is now being resolved (1Plow E.F. Haas T.A. Zhang L. Loftus J. Smith J.W. J. Biol. Chem. 2000; 275: 21785-21788Abstract Full Text Full Text PDF PubMed Scopus (1125) Google Scholar, 2Calderwood D.A. Shattil S.J. Ginsberg M.H. J. Biol. Chem. 2000; 275: 22607-22610Abstract Full Text Full Text PDF PubMed Scopus (413) Google Scholar, 3Harris E.S. McIntyre T.M. Prescott S.M. Zimmerman G. J. Biol. Chem. 2000; 275: 23409-23412Abstract Full Text Full Text PDF PubMed Scopus (273) Google Scholar, 4Kolanus W. Seed B. Curr. Opin. Cell Biol. 1997; 9: 725-731Crossref PubMed Scopus (128) Google Scholar, 5Burridge K. Chrzanowska-Wodnicka M. Annu. Rev. Cell Dev. Biol. 1996; 12: 463-518Crossref PubMed Scopus (1662) Google Scholar, 6Schlaepfer D. Hunter T. Trends Cell Biol. 1998; 8: 365-393Abstract Full Text Full Text PDF PubMed Scopus (439) Google Scholar). This review will concentrate on an emerging area of study: how the type of adhesion and the signaling following integrin ligation may be modulated by lateral interactions with other membrane components. This may occur through direct or indirect interactions. Two major groups of transmembrane proteins will form the focus of this review. One group, the tetraspans or TM4SF proteins (7Maecker H.T. Todd S.C. Levy S. FASEB J. 1997; 11: 428-442Crossref PubMed Scopus (812) Google Scholar, 8Hemler M.E. Mannion B.A. Berditchevski F. Biochim. Biophys. Acta. 1996; 1287: 67-71PubMed Google Scholar, 9Hemler M. Curr. Opin. Cell Biol. 1998; 10: 578-585Crossref PubMed Scopus (321) Google Scholar), is composed of transmembrane proteins implicated in regulation of cell migration and invasion. They can interact directly with the extracellular domain of the α chain of specific integrins. The second group, the syndecans (10Bernfield M. Gotte M. Park P.W. Reizes O. Fitzgerald M.L. Lincecum J. Zako M. Annu. Rev. Biochem. 1999; 68: 729-778Crossref PubMed Scopus (2330) Google Scholar, 11David G. FASEB J. 1993; 7: 1023-1030Crossref PubMed Scopus (374) Google Scholar, 12Carey D.J. Biochem. J. 1997; 327: 1-16Crossref PubMed Scopus (606) Google Scholar, 13Gallagher J.T. Biochem. Soc. Trans. 1997; 25: 1206-1209Crossref PubMed Scopus (57) Google Scholar, 14Woods A. Couchman J.R. Trends Cell Biol. 1998; 8: 189-192Abstract Full Text Full Text PDF PubMed Scopus (169) Google Scholar, 15Rapraeger A.C. Ott V.L. Curr. Opin. Cell Biol. 1998; 10: 620-628Crossref PubMed Scopus (101) Google Scholar), has not been shown to bind integrins directly but to bind to separate domains within integrin ligands. These also modify integrin-based adhesion, migration, invasiveness, and matrix assembly. The similarities in integrin modulation will be discussed. Because of space constraints, integrin interactions with other transmembrane proteins will only be briefly mentioned. The first integrin-associated transmembrane protein (IAP,1 CD47) was cloned in 1993 (16Lindberg F.P. Gresham H.D. Schwarz E. Brown E.J. J. Cell Biol. 1993; 123: 485-496Crossref PubMed Scopus (307) Google Scholar). This is a receptor for the cell-binding domain of thrombospondin (17Gao A.-G. Lindberg F.P. Finn M.B. Blystone S.D. Brown E.J. Frazier W.A. J. Cell Biol. 1996; 271: 21-24Scopus (332) Google Scholar), and it can regulate vitronectin binding to αvβ3 (16Lindberg F.P. Gresham H.D. Schwarz E. Brown E.J. J. Cell Biol. 1993; 123: 485-496Crossref PubMed Scopus (307) Google Scholar, 18Gao A.-G. Lindberg F.P. Dimitry J.M. Brown E.J. Frazier W.A. J. Cell Biol. 1996; 135: 533-544Crossref PubMed Scopus (186) Google Scholar) and activate αIIbβ3 through thrombospondin binding (19Chung J. Gao A.-G. Frazier W.A. J. Biol. Chem. 1997; 272: 14740-14746Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar). Mice lacking IAP have decreased resistance to bacterial infection probably because of delayed neutrophil migration to the site of infection and defective activation (20Lindberg F.P. Bullard D.C. Caver T.E. Gresham H.D. Beaudet A.L. Brown E.J. Science. 1996; 274: 795-798Crossref PubMed Scopus (303) Google Scholar). IAP may also interact with α2β1 integrin in vascular smooth muscle cells (21Wang X.-Q. Frazier W.A. Mol. Biol. Cell. 1998; 9: 865-874Crossref PubMed Scopus (140) Google Scholar). Second, integrin and growth factor signaling pathways intersect, and a subset of highly phosphorylated platelet-derived growth factor and insulin receptors, together with other downstream signaling components, coprecipitates with αvβ3 after treatment of cells with platelet-derived growth factor or insulin (22Schneller M. Vuori K. Ruoslahti E. EMBO J. 1997; 16: 5600-5607Crossref PubMed Scopus (427) Google Scholar). Third, urokinase plasminogen activator receptor (CD87) co-immunoprecipitates with β1, β2, and β3 integrins (23Wei Y. Mizukami I. Todd R.F. Petty H.R. Cancer Res. 1997; 57: 1682-1689PubMed Google Scholar). Other membrane molecules (reviewed in Ref. 9Hemler M. Curr. Opin. Cell Biol. 1998; 10: 578-585Crossref PubMed Scopus (321) Google Scholar) shown to interact by co-immunoprecipitation are CD98 (with α3β1), which may regulate β1integrin activation (24Fenczik C.A. Sethi T. Ramos J.W. Hughes P.E. Ginsberg M.H. Nature. 1997; 390: 81-85Crossref PubMed Scopus (260) Google Scholar), CD36 (with αIIbβ3), and CD46 (with α3β1). It is not yet clear whether interactions seen by co-immunoprecipitation are direct or due to formation of membrane microdomains containing multiple components, but some cross-linking studies (reviewed in Refs. 7Maecker H.T. Todd S.C. Levy S. FASEB J. 1997; 11: 428-442Crossref PubMed Scopus (812) Google Scholar, 8Hemler M.E. Mannion B.A. Berditchevski F. Biochim. Biophys. Acta. 1996; 1287: 67-71PubMed Google Scholar, 9Hemler M. Curr. Opin. Cell Biol. 1998; 10: 578-585Crossref PubMed Scopus (321) Google Scholar, 10Bernfield M. Gotte M. Park P.W. Reizes O. Fitzgerald M.L. Lincecum J. Zako M. Annu. Rev. Biochem. 1999; 68: 729-778Crossref PubMed Scopus (2330) Google Scholar) indicate direct binding. In addition, EMMPRIN/basigin (CD147), which regulates matrix metalloproteinase production, co-immunoprecipitates and colocalizes with α3β1 and α6β1 integrins (25Berditchevski F. Chang S. Bodorova J. Hemler M.E. J. Biol. Chem. 1997; 272: 29174-29180Abstract Full Text Full Text PDF PubMed Scopus (244) Google Scholar) and can be cross-linked to these at the cell surface. The dystrophin complex can also associate with β1 integrins, possibly through α and γ sarcoglycan (26Yoshida T. Pan Y. Hanada H. Iwata Y. Shigekawa M. J. Biol. Chem. 1998; 273: 1583-1590Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar). Finally, several studies (Ref. 27Iida J. T.A. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google and but not cell adhesion a transmembrane in in in the can bind directly to an can cell adhesion J. T.A. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar). are a family of transmembrane which have transmembrane and and extracellular (reviewed in H.T. Todd S.C. Levy S. FASEB J. 1997; 11: 428-442Crossref PubMed Scopus (812) Google Scholar, 8Hemler M.E. Mannion B.A. Berditchevski F. Biochim. Biophys. Acta. 1996; 1287: 67-71PubMed Google Scholar, 9Hemler M. Curr. Opin. Cell Biol. 1998; 10: 578-585Crossref PubMed Scopus (321) Google Scholar). The transmembrane domains are the highly between family the of and the of are also in the between transmembrane domains and a together with a and the of in the extracellular domain form the for the family (7Maecker H.T. Todd S.C. Levy S. FASEB J. 1997; 11: 428-442Crossref PubMed Scopus (812) Google Scholar, 8Hemler M.E. Mannion B.A. Berditchevski F. Biochim. Biophys. Acta. 1996; 1287: 67-71PubMed Google Scholar, 9Hemler M. Curr. Opin. Cell Biol. 1998; 10: 578-585Crossref PubMed Scopus (321) Google Scholar). The extracellular domains of are between family for some of are between to this is the which is between and J. T.A. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar). are and can interact with other and a of other cell components. Because of the have been or molecules (7Maecker H.T. Todd S.C. Levy S. FASEB J. 1997; 11: 428-442Crossref PubMed Scopus (812) Google Scholar, 8Hemler M.E. Mannion B.A. Berditchevski F. Biochim. Biophys. Acta. 1996; 1287: 67-71PubMed Google Scholar). are and are to or cells (reviewed in Refs. 7Maecker H.T. Todd S.C. Levy S. FASEB J. 1997; 11: 428-442Crossref PubMed Scopus (812) Google Scholar, 8Hemler M.E. Mannion B.A. Berditchevski F. Biochim. Biophys. Acta. 1996; 1287: 67-71PubMed Google Scholar, 9Hemler M. Curr. Opin. Cell Biol. 1998; 10: 578-585Crossref PubMed Scopus (321) Google Scholar). proteins and implicated in in adhesion, or (7Maecker H.T. Todd S.C. Levy S. FASEB J. 1997; 11: 428-442Crossref PubMed Scopus (812) Google Scholar, 8Hemler M.E. Mannion B.A. Berditchevski F. Biochim. Biophys. Acta. 1996; 1287: 67-71PubMed Google Scholar, 9Hemler M. Curr. Opin. Cell Biol. 1998; 10: 578-585Crossref PubMed Scopus (321) Google Scholar). cells and and in M. K. T. T. Cancer Res. 1996; Google Scholar). They also may in the is for formation of is and the of by and cells with the (reviewed in Refs. 7Maecker H.T. Todd S.C. Levy S. FASEB J. 1997; 11: 428-442Crossref PubMed Scopus (812) Google Scholar, 8Hemler M.E. Mannion B.A. Berditchevski F. Biochim. Biophys. Acta. 1996; 1287: 67-71PubMed Google Scholar, 9Hemler M. Curr. Opin. Cell Biol. 1998; 10: 578-585Crossref PubMed Scopus (321) Google Scholar). F. G. Hemler M.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar) to interact with integrins. The is in Ginsberg M.H. Biochem. J. 1997; 327: PubMed Scopus Google Scholar), and of adhesion because it in cells in F. K. Hemler M.E. J. Biol. Chem. 1997; 272: Full Text Full Text PDF PubMed Scopus Google Scholar). studies have co-immunoprecipitation and cross-linking and have interactions with and αIIbβ3 with cell or for or in Refs. 7Maecker H.T. Todd S.C. Levy S. FASEB J. 1997; 11: 428-442Crossref PubMed Scopus (812) Google Scholar, 8Hemler M.E. Mannion B.A. Berditchevski F. Biochim. Biophys. Acta. 1996; 1287: 67-71PubMed Google Scholar, 9Hemler M. Curr. Opin. Cell Biol. 1998; 10: 578-585Crossref PubMed Scopus (321) Google Scholar). studies indicate interact through the extracellular domain of the α F. K. Hemler M.E. J. Biol. Chem. 1997; 272: Full Text Full Text PDF PubMed Scopus Google Scholar, Berditchevski F. Hemler M.E. Mol. Cell. Biol. 1998; 9: Scopus Google Scholar), interactions may some Ginsberg M.H. Biochem. J. 1997; 327: PubMed Scopus Google Scholar), and the may also α6β1 not F. G. Hemler M.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, F. Hemler M.E. Mol. Biol. Cell. 1996; 7: PubMed Scopus Google Scholar). Integrins and in at of cells or in after cell I. Bodorova J. Berditchevski F. Hemler M.E. J. Biol. Chem. 1997; 272: Full Text Full Text PDF PubMed Scopus Google Scholar, F. G. Hemler M.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, Ginsberg M.H. Biochem. 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Biochem. 1999; 68: 729-778Crossref PubMed Scopus (2330) Google Scholar, 11David G. FASEB J. 1993; 7: 1023-1030Crossref PubMed Scopus (374) Google Scholar, 12Carey D.J. Biochem. J. 1997; 327: 1-16Crossref PubMed Scopus (606) Google Scholar, 13Gallagher J.T. Biochem. Soc. Trans. 1997; 25: 1206-1209Crossref PubMed Scopus (57) Google Scholar, 14Woods A. Couchman J.R. Trends Cell Biol. 1998; 8: 189-192Abstract Full Text Full Text PDF PubMed Scopus (169) Google Scholar, 15Rapraeger A.C. Ott V.L. Curr. Opin. Cell Biol. 1998; 10: 620-628Crossref PubMed Scopus (101) Google Scholar). The syndecans have cell and M. Mol. Biol. Cell. PubMed Scopus Google Scholar). and are the major syndecans of and is a of proteins in to which is not of the proteins have in the transmembrane In addition, syndecans have and to the are also highly have these and A. Couchman J.R. Trends Cell Biol. 1998; 8: 189-192Abstract Full Text Full Text PDF PubMed Scopus (169) Google Scholar). In between these is a to but between This has to of syndecans and A. Couchman J.R. Trends Cell Biol. 1998; 8: 189-192Abstract Full Text Full Text PDF PubMed Scopus (169) Google A.C. Ott V.L. Curr. Opin. Cell Biol. 1998; 10: 620-628Crossref PubMed Scopus (101) Google Scholar). The extracellular domains are highly for the (10Bernfield M. Gotte M. Park P.W. Reizes O. Fitzgerald M.L. Lincecum J. Zako M. Annu. Rev. Biochem. 1999; 68: 729-778Crossref PubMed Scopus (2330) Google Scholar, 11David G. FASEB J. 1993; 7: 1023-1030Crossref PubMed Scopus (374) Google Scholar, 12Carey D.J. Biochem. J. 1997; 327: 1-16Crossref PubMed Scopus (606) Google Scholar, 13Gallagher J.T. Biochem. Soc. Trans. 1997; 25: 1206-1209Crossref PubMed Scopus (57) Google Scholar, 14Woods A. Couchman J.R. Trends Cell Biol. 1998; 8: 189-192Abstract Full Text Full Text PDF PubMed Scopus (169) Google Scholar, 15Rapraeger A.C. Ott V.L. Curr. Opin. Cell Biol. 1998; 10: 620-628Crossref PubMed Scopus (101) Google Scholar), for the of and of tetraspans and transmembrane interactions between family interactions with with with extracellular matrix in a can bind a of extracellular matrix growth and through (10Bernfield M. Gotte M. Park P.W. Reizes O. Fitzgerald M.L. Lincecum J. Zako M. Annu. Rev. Biochem. 1999; 68: 729-778Crossref PubMed Scopus (2330) Google Scholar, 11David G. FASEB J. 1993; 7: 1023-1030Crossref PubMed Scopus (374) Google Scholar, 12Carey D.J. Biochem. J. 1997; 327: 1-16Crossref PubMed Scopus (606) Google Scholar, 13Gallagher J.T. Biochem. Soc. Trans. 1997; 25: 1206-1209Crossref PubMed Scopus (57) Google Scholar, 14Woods A. Couchman J.R. Trends Cell Biol. 1998; 8: 189-192Abstract Full Text Full Text PDF PubMed Scopus (169) Google Scholar, 15Rapraeger A.C. Ott V.L. Curr. Opin. Cell Biol. 1998; 10: 620-628Crossref PubMed Scopus (101) Google Scholar). This has to being for cell binding and of a of ligands (10Bernfield M. Gotte M. Park P.W. Reizes O. Fitzgerald M.L. Lincecum J. Zako M. Annu. Rev. Biochem. 1999; 68: 729-778Crossref PubMed Scopus (2330) Google Scholar). in and signaling are only now being with syndecans have can adhesion was the first to be cloned and has been the of in in decreased of W. J. Biol. Chem. 1998; 273: Full Text Full Text PDF PubMed Scopus Google Scholar), of in cells in the cells and M. S. H. M. Mol. Biol. Cell. PubMed Scopus Google Scholar). This with a of and of in of S. K. F. M. J. Cell 1996; Google Scholar). can be a for H. M. J. PubMed Scopus Google Scholar). in to cell and and the with but was not the focal (reviewed in Ref. 12Carey D.J. Biochem. J. 1997; 327: 1-16Crossref PubMed Scopus (606) Google Scholar). and can with the with the D.J. Biochem. J. 1997; 327: 1-16Crossref PubMed Scopus (606) Google Scholar). also in A. A. J.T. Couchman J.R. J. 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Chem. 1997; 272: Full Text Full Text PDF PubMed Scopus Google Scholar). This of the protein A. Couchman J.R. Mol. Biol. Cell. PubMed Scopus Google Scholar), which is a of syndecans (10Bernfield M. Gotte M. Park P.W. Reizes O. Fitzgerald M.L. Lincecum J. Zako M. Annu. Rev. Biochem. 1999; 68: 729-778Crossref PubMed Scopus (2330) Google Scholar, 11David G. FASEB J. 1993; 7: 1023-1030Crossref PubMed Scopus (374) Google Scholar, 12Carey D.J. Biochem. J. 1997; 327: 1-16Crossref PubMed Scopus (606) Google Scholar, 13Gallagher J.T. Biochem. Soc. Trans. 1997; 25: 1206-1209Crossref PubMed Scopus (57) Google Scholar, 14Woods A. Couchman J.R. Trends Cell Biol. 1998; 8: 189-192Abstract Full Text Full Text PDF PubMed Scopus (169) Google Scholar, 15Rapraeger A.C. Ott V.L. Curr. Opin. Cell Biol. 1998; 10: 620-628Crossref PubMed Scopus (101) Google Scholar). 4,5-bisphosphate the of the domain of A. Couchman J.R. J. Biol. Chem. 1997; 272: Full Text Full Text PDF PubMed Scopus Google Scholar, A. 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