Kabarowski, Janusz H. S. and Feramisco, Jamison D. and Le, Lu Q. and Gu, Jennifer L. and Luoh, Shiuh-Wen and Simon, Melvin I. and Witte, Owen N. (2000) Direct genetic demonstration of Galpha 13 coupling to the orphan G protein-coupled receptor G2A leading to RhoA-dependent actin rearrangement. Proceedings of the National Academy of Sciences of the United States of America, 97 (22). pp. 12109-12114. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:KABpnas00
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G2A is an orphan G protein-coupled receptor (GPCR), expressed predominantly in T and B cells and homologous to a small group of GPCRs of unknown function expressed in lymphoid tissues. G2A is transcriptionally induced in response to diverse stimuli, and its ectopic expression suppresses transformation of B lymphoid precursors by BCR-ABL. G2A induces morphological transformation of NIH 3T3 fibroblasts. Microinjection of constructs encoding G2A into Swiss 3T3 fibroblasts induces actin reorganization into stress fibers that depends on RhoA, but not CDC42 or RAC. G2A elicits RhoA-dependent transcriptional activation of serum response factor. Direct evaluation of RhoA activity demonstrates elevated levels of RhoA-GTP in G2A-expressing cells. Microinjection of embryonic fibroblasts derived from various Galpha knockout mice establishes a requirement for Galpha 13 but not Galpha 12 or Galpha q/11 in G2A-induced actin rearrangement. In conclusion, G2A represents a family of GPCRs expressed in lymphocytes that may link diverse stimuli to cytoskeletal reorganization and transcriptional activation through a pathway involving Galpha 13 and RhoA.
|Additional Information:||Copyright © 2000 by the National Academy of Sciences Contributed by Owen N. Witte, August 22, 2000 We thank Jamie White and Shirley Quan for assistance in the preparation of this manuscript, Dr. James Feramisco (University of California, San Diego) for helpful discussions, critical review of the manuscript, and use of the microinjection facility, and Brian Smith and Matt Zimmerman for their help and advice with microinjection. We also thank Drs. Richard Waldren and Lutz Birnbaumer for critical review of the manuscript. O.N.W. is an Investigator of the Howard Hughes Medical Institute, J.H.S.K. is a Fellow of the Leukemia and Lymphoma Society, and L.Q.L. is supported by a National Institutes of Health training grant (5-T32-CA009120–25). These studies were supported by National Cancer Institute Grant CA76204 to O.N.W. and National Institutes of Health Grant GM34236 to M.I.S. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. §1734 solely to indicate this fact.|
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|Deposited On:||30 Sep 2005|
|Last Modified:||14 Nov 2014 19:18|
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