THE CATALYTIC ACTIVITY OF SRC IS DISPENSABLE FOR TRANSLOCATION TO FOCAL ADHESIONS BUT CONTROLS THE TURNOVER OF THESE STRUCTURES DURING CELLMOTILITY

The Src family of protein tyrosine kinases is involved in transducing signals at sites of cellular adhesion. In particular, the v-Src oncopr otein resides in cellular focal adhesions, where it induces tyrosine p hosphorylation of pp125(FAK) and focal adhesion loss during transforma tion, v-Src is translocated to cellular focal adhesions by an actin-de pendent process. Here we have used mutant v-Src proteins that are temp erature-dependent for translocation, but,vith secondary mutations that render them constitutively kinase-inactive or myristylation-defective , to show that neither v-Src kinase activity nor a myristyl group are required to induce association of v-Src with actin stress fibres and r edistribution to sites of focal adhesions at the stress fibre termini. Moreover, switching the constitutively kinase-inactive or myristylati on-defective temperature-sensitive v-Src proteins to the permissive te mperature resulted in concomitant association with tyrosine-phosphoryl ated focal adhesion kinase (pp125(FAK)) and redistribution of both to focal adhesions, However, both catalytic activity and myristylation-me diated membrane association are required to induce dissociation of pp1 25(FAK) from v-Src, later degradation of pp125(FAK) and focal adhesion turnover during transformation and cell motility, These observations provide strong evidence that the role of the tyrosine kinase activity of the Src family at sites of cellular focal adhesions is to regulate the turnover of these structures during cell motility.