Regulation of Integrin Structure and Function

Small molecule antagonists have been used to obtain important insights into the conformational regulation of integrin structure and function (Shimaoka and Springer, 2003). The ability of ligands and ligand-mimetic... 

Shimaoka, M., Takagi, J., and Springer, T. A. (2002). Conformational regulation of integrin structure and function. Anna. Rev. Biophys. Biomol. Struct. 31, 485—516. 

The Rho family of small GTP-binding proteins functions to regulate the assembly of distinct actin structures in cells Rho regulates stress fiber assembly, Rac regulates lamellipodia protrusion and Cdc42 stimulates protrusion of the plasma membrane to form filopodia (Ridley and Hall, 1992 Ridley et at., 1992 Nobes and Hall, 1995 Kozma et at., 1995). All three regulate attachment of cells to the extracellular matrix via adhesive integrin structures (Nobes and Hall, 1995). 

Whether on natural or synthetic materials, cell adhesion is mediated by protein interactions with cell surface receptors. There are several classes of cell surface receptors, and this chapter will discuss integrins, selectins, and immunoglobulins. These receptors bind their ligands with high affinity and specificity, and while each receptor family regulates separate cellular functions, there is some overlap between families. Each of these receptor families possesses a characteristic molecular structure, with every receptor... 

Despite this complexity, most integrins share two, key interrelated functions first, to promote the assembly and organization of the actin cytoskeleton [122, 123] and second, to regulate signal transduction cascades [124-126], Spanning the cell membrane, these subunits serve as a communication pathway, linking the actin cytoskeleton and intracellular cytoplasmic proteins involved in focal adhesion complexes (FACs) with the cell s dynamic extracellular environment (Fig. 8) [127-130]. There are at least 50 distinct proteins known to be involved in FACs. Actin [131], vinculin, talin, tensin, a-actinin, and filamin provide a structural role, while focal adhesion kinase [132], integrin-linked kinase, Src-family kinase, PINCH, paxillin... 

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