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The Regulation of Growth and Intracellular Signaling by Integrins

The Scripps Research Institute, Department of Vascular Biology La Jolla, California 92037

Correspondence: Address reprint requests to: Martin A. Schwartz, Ph.D., Department of Vascular Biology, Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, California 92037.

Abstract

I. Introduction: INTEGRINS are a family of more than 20 different transmembrane receptors composed of noncovalently associated - and β-subunit heterodimers (1). Twelve different -subunits, each approximately 1000 residues in length, and eight different β-subunits, each approximately 750 residues, have been identified. The receptor consists of a very large extracellular domain, a transmembrane region, and a relatively short cytoplasmic region. The extracellular domain binds to various ligands including extracellular matrix (ECM) proteins, such as fibronectin (FN), vitronectin (VN), and collagen (Col), and to other cell surface receptors such as ICAM-1 (intercellular adhesion molecule) and VCAM-1 (vascular cell adhesion molecule). The receptor cytoplasmic domains interact with cytoskeletal proteins.

In addition to their role as adhesion receptors, integrins also function as signaling receptors and have been shown to regulate reorganization of the cytoskeleton, intracellular ion transport, lipid metabolism, kinase activation, and gene expression. In this review we will discuss the diverse integrinmediated signals presently known, with emphasis on the integrin-mediated signals that regulate cell growth and survival. For a discussion of integrin-mediated regulation of cell migration, differentiation, and integrin-ligand binding, the reader is referred to other integrin reviews (2–6).

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