Vj. Fincham et Mc. Frame, THE CATALYTIC ACTIVITY OF SRC IS DISPENSABLE FOR TRANSLOCATION TO FOCAL ADHESIONS BUT CONTROLS THE TURNOVER OF THESE STRUCTURES DURING CELLMOTILITY, EMBO journal, 17(1), 1998, pp. 81-92
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.