TY - JOUR
T1 - Regulation of FcεRI-mediated signaling by an adaptor protein STAP-2/BSK in rat basophilic leukemia RBL-2H3 cells
AU - Yamamoto, Tetsuya
AU - Yumioka, Taro
AU - Sekine, Yuichi
AU - Sato, Noriko
AU - Minoguchi, Mayu
AU - Yoshimura, Akihiko
AU - Matsuda, Tadashi
N1 - Funding Information:
This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture in Japan, the Osaka Foundation for Promotion of Clinical Immunology, the Akiyama Foundation, the Suhara Memorial Foundation, Mochida Memorial Foundation for Medical and Pharmceutical Research, and Uehara Memorial Foundation.
PY - 2003/7/4
Y1 - 2003/7/4
N2 - Crosslinking of multivalent antigen bound IgE transduces FcεRI mediated signaling cascades, which activate nonreceptor-type protein-tyrosine kinases and subsequent tyrosine phosphorylation of cellular proteins, and these are critical elements for degranulation in mast cells. We cloned a novel adaptor molecule, signal transducing adaptor protein (STAP)-2 containing PH and SH2-like domains as a c-fms interacting protein. STAP-2 was identical to a recently cloned adaptor molecule, BKS, a substrate of BRK (breast tumor kinase) tyrosine kinase, although its function is still unknown. To examine a novel function of STAP-2/BSK, we expressed STAP-2/BSK or its mutants in rat basophilic leukemia RBL-2H3 cells. Overexpression of STAP-2/BSK resulted in a suppression of FcεRI-mediated calcium mobilization and degranulation. FcεRI-induced tyrosine phosphorylation of phospholipase C-γ (PLC-γ) but not Syk was significantly suppressed in these cells. Furthermore, STAP-2/BSK associated with PLC-γ in vivo. These data indicate that STAP-2/BSK negatively controls the FcεRI-mediated calcium mobilization and degranulation by direct modulation of tyrosine phosphorylation of PLC-γ.
AB - Crosslinking of multivalent antigen bound IgE transduces FcεRI mediated signaling cascades, which activate nonreceptor-type protein-tyrosine kinases and subsequent tyrosine phosphorylation of cellular proteins, and these are critical elements for degranulation in mast cells. We cloned a novel adaptor molecule, signal transducing adaptor protein (STAP)-2 containing PH and SH2-like domains as a c-fms interacting protein. STAP-2 was identical to a recently cloned adaptor molecule, BKS, a substrate of BRK (breast tumor kinase) tyrosine kinase, although its function is still unknown. To examine a novel function of STAP-2/BSK, we expressed STAP-2/BSK or its mutants in rat basophilic leukemia RBL-2H3 cells. Overexpression of STAP-2/BSK resulted in a suppression of FcεRI-mediated calcium mobilization and degranulation. FcεRI-induced tyrosine phosphorylation of phospholipase C-γ (PLC-γ) but not Syk was significantly suppressed in these cells. Furthermore, STAP-2/BSK associated with PLC-γ in vivo. These data indicate that STAP-2/BSK negatively controls the FcεRI-mediated calcium mobilization and degranulation by direct modulation of tyrosine phosphorylation of PLC-γ.
KW - High affinity receptor for IgE
KW - Phospholipase C-γ
KW - Signal transducing adaptor protein-2
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U2 - 10.1016/S0006-291X(03)01042-8
DO - 10.1016/S0006-291X(03)01042-8
M3 - Article
C2 - 12810085
AN - SCOPUS:0042131586
SN - 0006-291X
VL - 306
SP - 767
EP - 773
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -