Direct genetic demonstration of G alpha 13 coupling to the orphan G protein-coupled receptor G2A leading to RhoA-dependent actin rearrangement
| Autor: | Melvin I. Simon, Owen N. Witte, Janusz H. Kabarowski, Jamison D. Feramisco, Lu Q. Le, Shiuh Wen Luoh, Jennifer L. Gu |
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| Rok vydání: | 2000 |
| Předmět: |
Transcriptional Activation
RHOA chemical and pharmacologic phenomena Cell Cycle Proteins Receptors Cell Surface GPR132 complex mixtures Cell Line Receptors G-Protein-Coupled Mice GTP-binding protein regulators GTP-Binding Proteins Serum response factor parasitic diseases Animals Humans Cytoskeleton Actin G protein-coupled receptor Multidisciplinary biology Biological Sciences Molecular biology Actins Cell biology biology.protein Ectopic expression rhoA GTP-Binding Protein |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 97(22) |
| ISSN: | 0027-8424 |
| Popis: | 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 G alpha knockout mice establishes a requirement for G alpha 13 but not G alpha 12 or G alpha 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 G alpha 13 and RhoA. |
| Databáze: | OpenAIRE |
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