Direct genetic demonstration of G alpha 13 coupling to the orphan G protein-coupled receptor G2A leading to RhoA-dependent actin rearrangement

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 funct ion expressed in lymphoid tissues. G2A is transcriptionally induced in resp onse to diverse stimuli, and its ectopic expression suppresses transformati on of B lymphoid precursors by BCR-ABL. G2A induces morphological transform ation of NIH 3T3 fibroblasts. Microinjection of constructs encoding G2A int o Swiss 3T3 fibroblasts induces actin reorganization into stress fibers tha t depends on RhoA, but not CDC42 or RAG, G2A elicits RhoA-dependent transcr iptional activation of serum response factor. Direct evaluation of RhoA act ivity demonstrates elevated levels of RhoA-GTP in G2A-expressing cells. Mic roinjection 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 fa mily of GPCRs expressed in lymphocytes that may link diverse stimuli to cyt oskeletal reorganization and transcriptional activation through a pathway i nvolving G alpha 13 and RhoA.