beta(3)-Integrin cytoplasmic binding proteins.

Abstract

Integrins are cell-surface adhesion receptors that play an important role in mediating numerous physiological processes,including inflammation, migration, adhesion, and proliferation. Integrin regulation by events within the cell has been termed "inside-out " signaling; this is a capacity that is unique to integrin receptors. As is typical of other cell-surface receptors, integrins can also transduce signals from outside the cell into the cytoplasm on binding extracellular ligands ("outside-in signaling "). Integrins are composed of an alpha and a beta subunit, which form a heterodimer. The beta(3)-integrin family consists of alpha(IIb)beta(3)-found on platelets and megakaryocytes, and the more widely distributed alpha(v)beta(3). beta Subunits consist of a large extracellular domain, a single transmembrane segment, and a relatively short cytoplasmic tail. The cytoplasmic domains do not contain intrinsic tyrosine kinase activity, and therefore signaling occurs primarily via recruitment of intracellular signaling molecules. Integrins form transmembrane connections, and the interactions between integrin cytoplasmic domains, intracellular factors (cytoplasmic proteins and intracellular signaling pathways), and membrane-anchored proteins play an important role in integrin-mediated events. There are at least 21 proteins that associate with integrin beta tails to regulate cell motility, proliferation, differentiation, and apoptosis. In this review, we will focus on 10 of these proteins and their function in integrin-mediated events.