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Integrins

Updated 12/6/02

Integrins are cell adhesion molecules that are also bi-directional signalling molecules, that is they signal from the out side to the inside of cells, and vice versa (Calderwwod et al, 2000).  Integrins bind a number of cytoskeletal proteins, some of which are actin-binding proteins (see table 1), and some integrin types bind actin itself (Kieffer et al, 1995). 
Integrin-binding Protein Function References
actin microfilaments Kieffer et al, 1995; Calderwood et al, 2000
a-actinin Actin bundling protein Pavalko et al, 1991; Otey et al, 1993
Focal contact Adhesion kinase Signalling kinase
Paxillin
Plectin A giant actin and intermediate filament binding protein. Geerts et al, 1999
Talin An actin-binding protein, and a component of the focal contact. Calderwood et al, 2002
RACK1 Connects PKCe to integrin b chain Besson et al, 2002
Table 1    Integrin binding proteins

References:-

Besson, A., Wilson, T. L. & Yong, V. W. (2002) The anchoring protein RACK1 links protein kinase Ce to integrin b chains. Requirement for adhesion and motility. J.Biol.Chem. 277, 22073-22084.

Calderwood, D. A., Shattil, S. J. & Ginsberg, M. H. (2000) Integrins and actin filaments: Reciprocal regulation of cell adhesion and signaling., J.Biol.Chem. 275, 22607-22610.

Calderwood, D. A., Yan, B., de Pereda, J. M., Alvarez, B. G., Fujioka, Y., Liddington, R. C. & Ginsberg, M. H. (2002) The phosphotyrosine binding-like domain of talin activates integrins. J.Biol.Chem. 277, 21749-21758.

Defilippi, P., Venturino, M., Gulino, D., Duperray, A., Boquet, P., Fiorentini, C., Volpe, G., Palmieri, M., Silengo, L. & Tarone, G. (1997) Dissection of pathways implicated in integrin-mediated actin cytoskeleton assembly. J.Biol.Chem. 272, 21726-21734.

Geerts, D., Fontao, L., Nievers, M. J., Schaapveld, R. Q. J., Purkis, P. E., Wheeler, G. N., Lane, E. B., Leig, I. M. & Sonnenberg, A. (1999) Binding of integrin a6b4 to plectin prevents plectin association with F-actin but does not interfere with intermediate filament binding. J.Cell Biol. 147, 417-434.

Jones, S. L., Wang, J., Turck, C. W. & Brown, E. J. (1998) A role for actin-bundling protein L-plastin in the regulation of leukocyte integrin function. Proc.Nat.Acad.Sci. USA. 95, 9331-9336.

Kieffer, J. D., Plopper, G., Ingber, D. E., Hartwig, J. H. & Kupper, T. S. (1995) Direct binding of F actin to the cytoplasmic domain of the a2 intergrin chain in vitro. Biochem.Biophys.Res.Comm. 217, 466-474.

Laukaitis, C. M., Webb, D. J., Donais, K. & Horwitz, A. F. (2001) Differential dynamics of a5 integrin, paxillin, and a-actinin during formation and disassembly of adhesions in migrating cells., J. Cell Biol. 153, 1427-1440.

Löfgren, R., Ng-Sikorski, J., Sjölander, A. & Andersson, T. (1993) b2-integrin engagement triggers actin polymerization and phosphatidylinositol trisphosphate formation in non-adherent human neutrophils, J.Cell Biol. 123, 1597-1605.

Lub, M., van Kooyk, Y., van Vliet, S. J. & Figdor, C. G. (1997) Dual role of the actin cytoskleton in regulating cell adhesion mediated by the integrin lymphocyte function-associated molecule-1, Mol.Biol.Cell. 8, 341-351.

Ng-Sikorski, J., Lindén, L., Eierman, D., Franzen, L., Molony, L. & Andersson, T. (1996) Engagement of L-selectin impairs the actin polymerizing capacity of b2-integrins on neutrophils, J.Cell Sci. 109, 2361-2369.

Obergfell, A., Judd, B. A., del Pozo, M. A., Schwartz, M. A., Koretzky, G. A. & Shattil, S. J. (2001) The molecular adapter SLP-76 relays signals from platelet integrin aIIbb3 to the actin cytoskeleton., J.Biol.Chem. 276, 5916-5923.

Otey, C. A., Vasquez, G. B., Burridge, K. & Erickson, B. W. (1993) Mapping of the a-actinin binding site with the b1 integrin cytoplasmic domain, J. Biol. Chem. 268, 21193-21197.

Pavalko, F. M., Otey, C. A., Simon, K. O. & Burridge, K. (1991) Alpha-actinin: a direct link between actin and integrins, Biochem. Soc. Trans. 19, 1065-1069.

Toshima, J., Toshima, J. Y., Amano, T., Yang, N., Narumiya, S. & Mizuno, K. (2001) Cofilin phospholrylation by protein kinase testicular protein kinase 1 and its role in integrin-mediated actin reorganization and focal adhesion formation. Mol. Biol. of the Cell. 12, 1131-1145.

Toshima, J., Toshima, J. Y. & Mizuno, K. (2000) Cofilin phosphorylation by protein kinase TESK1 and its role in integrin-mediated actin remodeling, Molecular Biology of the Cell. 11, 915.

Wang, J., Chen, H. & Brown, E. J. (2001) L-plastin peptide activation of avb3-mediated adhesion requires integrin conformational change and actin filament disassembly., J.Biol.Chem. 276, 14474-14481.

 
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