Document Detail


Signal-transducing adaptor protein-2 regulates stromal cell-derived factor-1 alpha-induced chemotaxis in T cells.
MedLine Citation:
PMID:  19933863     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Yuichi Sekine; Osamu Ikeda; Satoshi Tsuji; Chikako Yamamoto; Ryuta Muromoto; Asuka Nanbo; Kenji Oritani; Akihiko Yoshimura; Tadashi Matsuda
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  183     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-12-16     Completed Date:  2010-02-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7966-74     Citation Subset:  AIM; IM    
Affiliation:
Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo, Japan.
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MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Signal Transducing / biosynthesis,  deficiency,  genetics,  physiology*
Adjuvants, Immunologic / biosynthesis,  deficiency,  genetics,  physiology
Animals
Cell Line, Tumor
Cells, Cultured
Chemokine CXCL12 / physiology*
Chemotaxis, Leukocyte / genetics,  immunology*
Humans
Jurkat Cells
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Phosphoproteins / biosynthesis,  deficiency,  genetics,  physiology*
Proto-Oncogene Proteins c-vav / metabolism,  physiology
Signal Transduction / immunology
T-Lymphocytes / cytology*,  immunology*,  metabolism
rac1 GTP-Binding Protein / metabolism,  physiology
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Adjuvants, Immunologic; 0/CXCL12 protein, human; 0/Chemokine CXCL12; 0/Phosphoproteins; 0/Proto-Oncogene Proteins c-vav; 0/RAC1 protein, human; 0/STAP2 protein, human; 0/VAV1 protein, human; EC 3.6.5.2/rac1 GTP-Binding Protein

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