Integrins play central roles in cell adhesion, migration, and tissue formation, and in the regulation of gene expression, cell growth, and the cytoskeleton. We are characterizing mechanisms of integrin signaling and function by (a) comparing components of different types of adhesion complexes and associated cytoskeletal molecules, (b) identifying regulators of the formation of these integrin complexes, (c) determining their roles in adhesion, migration, and extracellular matrix assembly, (d) characterizing roles of key cytoskeletal molecules, and (e) defining downstream signal transduction systems. Effects of expressing specific proteins and domains on cell biological functions are being characterized. A variety of constructs and molecular chimeras of individual cytoskeletal and signal transduction molecules and dominant-negative inhibitors are being tested as mediators or modulators of downstream steps in the hierarchies of responses to integrin receptors. Because integrin functions are crucial for normal embryonic development, wound healing, and differentiated tissue function, these studies provide an opportunity to identify new pathways as potential targets for diagnosis and therapy.
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