Premium
Integrin‐mediated signal transduction in cells lacking focal adhesion kinase p125 FAK
Author(s) -
Ueki Kazue,
Mimura Toshihide,
Nakamoto Tetsuya,
Sasaki Terukatsu,
Aizawa Shinichi,
Hirai Hisamaru,
Yano Shintaro,
Naruse Takuji,
Nojima Yoshihisa
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)00862-x
Subject(s) - focal adhesion , integrin , signal transduction , ptk2 , microbiology and biotechnology , adhesion , chemistry , biology , biochemistry , protein kinase c , receptor , mitogen activated protein kinase kinase , organic chemistry
We have previously shown that integrin‐dependent tyrosine phosphorylation of p130 Cas (Cas) could be induced in a mouse fibroblast cell line that does not express focal adhesion kinase p125 FAK (FAK). By analyzing FAK‐deficient (FAK−/−) cells transiently expressing Cas mutant proteins, we demonstrate here that the Src homology 3 (SH3) domain of Cas is indispensable for adhesion‐mediated Cas phosphorylation in this mutant cell line. While the FAK directly binds to Cas‐SH3, our findings imply that SH3‐binding molecule(s) other than FAK might regulate Cas phosphorylation, at least in FAK−/− cells. In this regard, we observed that FAK−/− cells expressed cell adhesion kinase β (CAKβ), a protein tyrosine kinase of the FAK subfamily. CAKβ expressed by FAK−/− cells was associated in vivo with Cas in a Cas‐SH3‐dependent manner. Moreover, integrin stimulation induces tyrosine phosphorylation of CAKβ in FAK−/− cells. Thus, our results suggest that CAKβ contributes to integrin‐mediated signal transduction in place of FAK in FAK‐deficient cells.