Direct genetic demonstration of Gα13 coupling to the orphan G protein-coupled receptor G2A leading to RhoA-dependent actin rearrangement

Janusz H S Kabarowski, Jamison D. Feramisco, Lu Q. Le, Jennifer L. Gu, Shiuh Wen Luoh, Melvin I. Simon, Owen N. Witte

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

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 Gα knockout mice establishes a requirement for Gα13 but not Gα12 or Gαq/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 Gα13 and RhoA.

Original languageEnglish (US)
Pages (from-to)12109-12114
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number22
DOIs
StatePublished - Oct 24 2000

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G-Protein-Coupled Receptors
Actins
Fibroblasts
Microinjections
Transcriptional Activation
Serum Response Factor
Stress Fibers
Lymphoid Tissue
Guanosine Triphosphate
Knockout Mice
B-Lymphocytes
Lymphocytes
T-Lymphocytes

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Direct genetic demonstration of Gα13 coupling to the orphan G protein-coupled receptor G2A leading to RhoA-dependent actin rearrangement. / Kabarowski, Janusz H S; Feramisco, Jamison D.; Le, Lu Q.; Gu, Jennifer L.; Luoh, Shiuh Wen; Simon, Melvin I.; Witte, Owen N.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 22, 24.10.2000, p. 12109-12114.

Research output: Contribution to journalArticle

Kabarowski, Janusz H S ; Feramisco, Jamison D. ; Le, Lu Q. ; Gu, Jennifer L. ; Luoh, Shiuh Wen ; Simon, Melvin I. ; Witte, Owen N. / Direct genetic demonstration of Gα13 coupling to the orphan G protein-coupled receptor G2A leading to RhoA-dependent actin rearrangement. In: Proceedings of the National Academy of Sciences of the United States of America. 2000 ; Vol. 97, No. 22. pp. 12109-12114.
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AU - Le, Lu Q.

AU - Gu, Jennifer L.

AU - Luoh, Shiuh Wen

AU - Simon, Melvin I.

AU - Witte, Owen N.

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