Abstract
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 revealed that STAP-2 regulates integrin-mediated T cell adhesion. In the present study, we find that STAP-2 expression affects Jurkat T cell migration after stromal cell-derived factor-1alpha (SDF-1alpha)-treatment. Furthermore, STAP-2-deficient T cells exhibit reduced cell migration after SDF-1alpha-treatment. Importantly, overexpression of STAP-2 in Jurkat T cells induces activation of small guanine triphosphatases, such as Rac1 and Cdc42. Regarding the mechanism for this effect, we found that STAP-2 associates with Vav1, the guanine-nucleotide exchanging factor for Rac1, and enhances downstream Vav1/Rac1 signaling. These results reveal a novel STAP-2-mediated mechanism for the regulation of SDF-1alpha-induced chemotaxis of T cells via activation of Vav1/Rac1 signaling.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / biosynthesis
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Adaptor Proteins, Signal Transducing / deficiency
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / physiology*
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Adjuvants, Immunologic / biosynthesis
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Adjuvants, Immunologic / deficiency
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Adjuvants, Immunologic / genetics
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Adjuvants, Immunologic / physiology
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Animals
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Cell Line, Tumor
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Cells, Cultured
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Chemokine CXCL12 / physiology*
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Chemotaxis, Leukocyte / genetics
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Chemotaxis, Leukocyte / immunology*
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Humans
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Jurkat Cells
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Phosphoproteins / biosynthesis
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Phosphoproteins / deficiency
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Phosphoproteins / genetics
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Phosphoproteins / physiology*
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Proto-Oncogene Proteins c-vav / metabolism
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Proto-Oncogene Proteins c-vav / physiology
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Signal Transduction / immunology
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T-Lymphocytes / cytology*
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism
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rac1 GTP-Binding Protein / metabolism
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rac1 GTP-Binding Protein / physiology
Substances
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Adaptor Proteins, Signal Transducing
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Adjuvants, Immunologic
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CXCL12 protein, human
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Chemokine CXCL12
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Phosphoproteins
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Proto-Oncogene Proteins c-vav
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RAC1 protein, human
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STAP2 protein, human
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VAV1 protein, human
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rac1 GTP-Binding Protein