Etk/BMX, a member of the Btk family of tyrosine kinases, is highly expresse
d in cells with great migratory potential, including endothelial cells and
metastatic carcinoma cell lines. Here, we present evidence that Etk is invo
lved in integrin signalling and promotes cell migration. The activation of
Etk by extracellular matrix proteins is regulated by FAK through an interac
tion between the PH domain of Etk and the FERM domain of FAK. The lack of E
tk activation by extracellular matrix in FAK-null cells could be restored b
y co-transfection with wild-type FAK, Disrupting the interaction between Et
k and FAK diminished the cell migration promoted by either kinase. Furtherm
ore, inhibiting Etk expression in metastatic carcinoma cell lines with an a
ntisense oligonucleotide blocks integrin-mediated migration of these cells.
Taken together, our data indicate the essential role of the interaction of
the PH domain of Etk and the FERM domain of FAK in integrin signalling.