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PNAS 104 (1): 145-150

Copyright © 2007 by the National Academy of Sciences.

BIOLOGICAL SCIENCES / CELL BIOLOGY

Bcl10 plays a critical role in NF-{kappa}B activation induced by G protein-coupled receptors

Donghai Wang*,{dagger}, Yun You*, Pei-Chun Lin*, Liquan Xue{ddagger}, Stephan W. Morris{ddagger}, Hu Zeng§, Renren Wen§, and Xin Lin*,¶

*Department of Molecular and Cellular Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030; {ddagger}Departments of Pathology and Hematology–Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105; and §Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI 53201

Edited by Michael Karin, University of California at San Diego School of Medicine, La Jolla, CA, and approved November 14, 2006

Received for publication March 9, 2006.

Abstract: 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-{kappa}B activation, the molecular mechanism by which GPCRs induced NF-{kappa}B activation remains largely unknown. Bcl10 is an essential adaptor molecule connecting antigen receptor signaling cascades to NF-{kappa}B 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-{kappa}B 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-{alpha}-, LPS-, and integrin-induced NF-{kappa}B activation was not affected in Bcl10-deficient cells. Together, our results provide genetic evidence showing that Bcl10 is a key signaling component mediating NF-{kappa}B activation induced by GPCRs in nonlymphoid cells.

Key Words: lysophosphatidic acid • signal transduction • endothelin-1

Author contributions: D.W. and Y.Y. contributed equally to this work; D.W. and X.L. designed research; D.W., Y.Y., P.-C.L., H.Z., and R.W. performed research; L.X. and S.W.M. contributed new reagents/analytic tools; D.W., Y.Y., P.-C.L., H.Z., R.W., and X.L. analyzed data; and D.W. and X.L. wrote the paper.

{dagger}Present address: The CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115.

The authors declare no conflict of interest.

This article is a PNAS direct submission.

This article contains supporting information online at www.pnas.org/cgi/content/full/0601894104/DC1.

To whom correspondence should be addressed. E-mail: xllin{at}mdanderson.org

© 2007 by The National Academy of Sciences of the USA

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