Signal-transducing adaptor protein-2 regulates stromal cell-derived factor-1 alpha-induced chemotaxis in T cells.
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.
Sekine
Yuichi
Y
Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo, Japan.
Ikeda
Osamu
O
Tsuji
Satoshi
S
Yamamoto
Chikako
C
Muromoto
Ryuta
R
Nanbo
Asuka
A
Oritani
Kenji
K
Yoshimura
Akihiko
A
Matsuda
Tadashi
T
D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000276:Adjuvants, Immunologic / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology*; D006801:Humans; D019169:Jurkat Cells; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051567:Proto-Oncogene Proteins c-vav / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D000276:Adjuvants, Immunologic; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D010750:Phosphoproteins; D051567:Proto-Oncogene Proteins c-vav; C107953:RAC1 protein, human; C413897:STAP2 protein, human; C496618:VAV1 protein, human; D020830:rac1 GTP-Binding Protein