PubMed Journals: Nat Cell Biol
Source: PMID: 11331870
⇦ ⇨ Nat Cell Biol. 2001 May;3(5):439-44.
Regulation of the PH-domain-containing tyrosine
kinase Etk by focal adhesion kinase through
the FERM domain.
Chen R(1), Kim O, Li M, Xiong X, Guan JL,
Kung HJ, Chen H, Shimizu Y, Qiu Y.
(1) Departments of Laboratory Medicine and
Pathology and Pharmacology, University of
Minnesota, Minneapolis, Minnesota 55455,
Etk/BMX, a member of the Btk family of tyrosine
kinases, is highly expressed in cells with
great migratory potential, including endothelial
cells and metastatic carcinoma cell lines.
Here, we present evidence that Etk is involved
in integrin signalling and promotes cell
migration. The activation of Etk by extracellular
matrix proteins is regulated by FAK through
an interaction between the PH domain of
Etk and the FERM domain of FAK. The lack
of Etk activation by extracellular matrix
in FAK-null cells could be restored by
co-transfection with wild-type FAK. Disrupting
the interaction between Etk and FAK diminished
the cell migration promoted by either kinase.
Furthermore, inhibiting Etk expression in
metastatic carcinoma cell lines with an
antisense 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.
DOI: 10.1038/35074500 PMID: 11331870 [Indexed