Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / deficiency
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Adaptor Proteins, Signal Transducing / immunology*
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Adaptor Proteins, Signal Transducing / metabolism
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Amino Acid Motifs / genetics
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Amino Acid Motifs / immunology
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Animals
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Cell Adhesion / genetics
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Cell Adhesion / immunology
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Fibronectins / immunology
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Fibronectins / metabolism
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Focal Adhesion Kinase 1 / genetics
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Focal Adhesion Kinase 1 / immunology*
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Focal Adhesion Kinase 1 / metabolism
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Humans
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Integrins / genetics
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Integrins / immunology
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Integrins / metabolism
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Jurkat Cells
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Mice
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Mice, Knockout
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Phosphoproteins / deficiency
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Phosphoproteins / immunology*
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Phosphoproteins / metabolism
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Proteasome Endopeptidase Complex / genetics
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Proteasome Endopeptidase Complex / immunology*
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Proteasome Endopeptidase Complex / metabolism
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Proto-Oncogene Proteins c-cbl / genetics
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Proto-Oncogene Proteins c-cbl / immunology
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Proto-Oncogene Proteins c-cbl / metabolism
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STAT2 Transcription Factor / genetics
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STAT2 Transcription Factor / immunology
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STAT2 Transcription Factor / metabolism
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STAT3 Transcription Factor / genetics
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STAT3 Transcription Factor / immunology
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STAT3 Transcription Factor / metabolism
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Signal Transduction / genetics
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Signal Transduction / immunology*
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism
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src Homology Domains / genetics
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src Homology Domains / immunology
Substances
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Adaptor Proteins, Signal Transducing
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Fibronectins
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Integrins
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Phosphoproteins
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STAP2 protein, human
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STAP2 protein, mouse
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STAT2 Transcription Factor
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STAT2 protein, human
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STAT3 Transcription Factor
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STAT3 protein, human
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Stat2 protein, mouse
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Stat3 protein, mouse
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Proto-Oncogene Proteins c-cbl
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Focal Adhesion Kinase 1
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PTK2 protein, human
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Ptk2 protein, mouse
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Proteasome Endopeptidase Complex
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CBL protein, human