Gene Regulation by Adhesion-dependent Signal Transduction Pathways

Normal cellular growth control reflects a carefully orchestrated series of signal transduction events that culminate in changes in gene expression. The proliferative response, in multicellular organisms, is initiated by environmental cues, contributed largely by growth factors, and adhesive influences, provided by the extracellular matrix (ECM). The integrin family of heterodimeric receptors mediates adhesion of cells to the ECM. Engagement of integrin receptors with extracellular ligands gives rise to the formation of complex multiprotein structures, termed focal adhesions, which link the ECM to the cytoplasmic actin cytoskeleton. In addition to providing a structural link between the cell and its underlying matrix, focal adhesions contain protein tyrosine kinases, which become activated as a result of cell interaction with the substrate and initiate adhesion-dependent signal transduction cascades culminating in changes in gene expression. In this review, I will consider the role of integrin-mediated signal transduction in regulating genetic changes necessary for controlled cellular proliferation.