TY - JOUR
T1 - Bcl10 plays a critical role in NF-κB activation induced by G protein-couple receptors
AU - Wang, Donghai
AU - You, Yun
AU - Lin, Pei Chun
AU - Xue, Liquan
AU - Morris, Stephan W.
AU - Zeng, Hu
AU - Wen, Renren
AU - Lin, Xin
PY - 2007/1/2
Y1 - 2007/1/2
N2 - G protein-coupled receptors (GPCRs) play pivotal roles in cell proliferation, differentiation, and survival. Although many studies indicate that the stimulation of GPCRs leads to NF-κB activation, the molecular mechanism by which GPCRs induced NF-κB activation remains largely unknown. Bcl10 is an essential adaptor molecule connecting antigen receptor signaling cascades to NF-κB activation in lymphocytes. However, the function of Bcl10 in nonlymphoid cells remains to be determined. In this study, we demonstrated that the deficiency of Bcl10 resulted in the defect in NF-κB activation induced by either expressing the constitutively active mutant of G protein or stimulation of cells with lysophosphatidic acid or endothelin-1, which activate their GPCR. In contrast, TNF-α-, LPS-, and integrin-induced NF-κB activation was not affected in Bcl10-deficient cells. Together, our results provide genetic evidence showing that Bcl10 is a key signaling component mediating NF-κB activation induced by GPCRs in nonlymphoid cells.
AB - G protein-coupled receptors (GPCRs) play pivotal roles in cell proliferation, differentiation, and survival. Although many studies indicate that the stimulation of GPCRs leads to NF-κB activation, the molecular mechanism by which GPCRs induced NF-κB activation remains largely unknown. Bcl10 is an essential adaptor molecule connecting antigen receptor signaling cascades to NF-κB activation in lymphocytes. However, the function of Bcl10 in nonlymphoid cells remains to be determined. In this study, we demonstrated that the deficiency of Bcl10 resulted in the defect in NF-κB activation induced by either expressing the constitutively active mutant of G protein or stimulation of cells with lysophosphatidic acid or endothelin-1, which activate their GPCR. In contrast, TNF-α-, LPS-, and integrin-induced NF-κB activation was not affected in Bcl10-deficient cells. Together, our results provide genetic evidence showing that Bcl10 is a key signaling component mediating NF-κB activation induced by GPCRs in nonlymphoid cells.
KW - Endothelin-1
KW - Lysophosphatidic acid
KW - Signal transduction
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U2 - 10.1073/pnas.0601894104
DO - 10.1073/pnas.0601894104
M3 - Article
C2 - 17179215
AN - SCOPUS:33846034844
SN - 0027-8424
VL - 104
SP - 145
EP - 150
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 1
ER -