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STAP‐2 regulates integrin‐mediated T‐cell adhesion through protein degradation of FAK
Author(s) -
Matsuda Tadashi,
Ikeda Osamu,
Sekine Yuichi
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1071.10
Subject(s) - focal adhesion , signal transducing adaptor protein , integrin , microbiology and biotechnology , ubiquitin ligase , chemistry , signal transduction , cell adhesion , ubiquitin , biology , cell , biochemistry , gene
Signal transducing adaptor protein‐2 (STAP‐2) is a recently identified adaptor protein that contains Pleckstrin and Src homology 2‐like domains as well as a YXXQ motif in its C‐terminal region. Our previous studies demonstrated that STAP‐2 binds to STAT3 and STAT5, and regulates their signaling pathways. In the present study, we find that STAP‐2‐deficient splenocytes or T‐cells exhibit enhanced cell adhesion to fibronectin (FN) after phorbol myristate acetate‐treatment, and that STAP‐2‐deficient splenocytes contain the increased protein contents of focal adhesion kinase (FAK). Furthermore, overexpression of STAP‐2 induces a dramatic decrease in the protein contents of FAK and integrin‐mediated T‐cell adherence to FN in Jurkat T‐cells via the degradation of FAK. Regarding the mechanism for this effect, we find that STAP‐2 associated with FAK and enhanced its degradation, proteasome inhibitors blocked FAK degradation, and STAP‐2 recruits an endogenous E3‐ubiquitin ligase, Cbl, to FAK. These results reveal a novel regulation mechanism for integrin‐mediated signaling in T‐cells via STAP‐2, which directly interacts with and degrades FAK.