MATRIX INTEGRIN INTERACTION ACTIVATES THE MITOGEN-ACTIVATED PROTEIN-KINASE, P44(ERK-1) AND P42(ERK-2)/

Cell adhesion to extracellular matrix proteins is a dynamic process le ading to dramatic changes in the cell phenotype. Integrins are one of the major receptor families that mediate cell-matrix contact. Evidence that integrins can act as signal transducing molecules has accumulate d over the past few years. We report here that p44(erk-1) and p42(erk- 2) mitogen-activated protein (MAP) kinases are rapidly phosphorylated on tyrosine residues upon adhesion of human skin fibroblasts to fibron ectin or upon cross-linking of beta 1 integrins with antibody. The tyr osine phosphorylation of both kinases is associated with increased enz ymatic activity. Pretreatment of the cells with cytochalasin D, which selectively disrupts the network of the actin filaments, completely in hibits this adhesion-mediated MAP kinase activation. Thus, our finding s indicate that ligation of beta 1 integrins induces an increase in bo th tyrosine phosphorylation and enzymatic activity of p44(erk-1) and p 42(erk-2) MAP kinases, and that the integrity of the actin cytoskeleto n is essential in this process. Since MAP kinase behaves as a converge nce point for diverse receptor-initiated signaling events at the plasm a membrane, this serine/threonine kinase plays a key role and helps to account for the diversity of integrin-dependent cell functions.