Signal-transducing adaptor protein-2 regulates integrin-mediated T cell adhesion through protein degradation of focal adhesion kinase.

Signal-transducing adaptor protein-2 (STAP-2) is a recently identified adaptor protein that contains pleckstrin homology- 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 after PMA treatment, and that STAP-2-deficient T cells 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 adhesion to fibronectin in Jurkat T cells via the degradation of FAK. Regarding the mechanism for this effect, we found that STAP-2 associates with FAK and enhances its degradation, proteasome inhibitors block 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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Amino Acid Motifs, Animals, Cell Adhesion, Fibronectins, Focal Adhesion Kinase 1, Humans, Integrins, Jurkat Cells, Mice, Mice, Knockout, Phosphoproteins, Proteasome Endopeptidase Complex, Proto-Oncogene Proteins c-cbl, STAT2 Transcription Factor, STAT3 Transcription Factor, Signal Transduction, T-Lymphocytes, src Homology Domains
J. Immunol.
Date: Aug. 15, 2007
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