Active ERK/MAP kinase is targeted to newly forming cell-matrix adhesions by integrin engagement and v-Src

Integrin engagement generates cellular signals leading to the recruitment o f structural and signalling molecules which, in concert with rearrangements of the actin cytoskeleton, leads to the formation of focal adhesion comple xes. Using antisera reactive either with total ERK or with phosphorylated/a ctivated forms of ERK, in rat embryo fibroblasts and embryonic avian cells that express v-Src, we found that active ERK is targeted to newly forming f ocal adhesions after integrin engagement or activation of v-Src. UO126, an inhibitor of MAP kinase kinase 1 (MEK1), suppressed focal adhesion targetin g of active ERK and cell spreading. Also, integrin engagement and v-Src ind uced myosin light chain kinase (MLCK)-dependent phosphorylation of myosin l ight chain downstream of the MEK/ERK pathway, and MLCK and myosin activitie s are required for the focal adhesion targeting of ERK. The translocation o f active ERK to newly forming focal adhesions may direct specificity toward s appropriate downstream targets that influence adhesion assembly. These fi ndings support a role for ERK in the regulation of the adhesion/ cytoskelet al network and provide an explanation for the role of ERK in fell motility.