Differential involvement of G alpha(12) and G alpha(13) in receptor-mediated stress fiber formation

The ubiquitously expressed heterotrimeric guanine nucleotide-binding protei ns (G-proteins) G(12) and G(13) have been shown to activate the small GTPas e Rho. Rho stimulation leads to a rapid remodeling of the actin cytoskeleto n and subsequent stress fiber formation. We investigated the involvement of G(12) or G(13) in stress fiber formation induced through a variety of G(q) /G(11)-coupled receptors. Using fibroblast cell lines derived from wildtype and G alpha(q)/G alpha(11)-deficient mice, we show that agonist-dependent activation of the endogenous receptors for thrombin or lysophosphatidic aci d and of the heterologously expressed bradykinin B-2, vasopressin V-1A, end othelin ETA, and serotonin 5-HT2C receptors induced stress fiber formation in either the presence or absence of G alpha(q)/G alpha(11). Stress fiber a ssembly induced through the muscarinic M-1 and the metabotropic glutamate s ubtype 1 alpha receptors was dependent on G(q)/G(11) proteins. The activati on of the G(q)/G(11)-coupled endothelin ETB and angiotensin AT,A receptors failed to induce stress fiber formation. Lysophosphatidic acid, B-2, and 5- HT2C receptor-mediated stress fiber formation was dependent on G alpha(13) and involved epidermal growth factor (EGF) receptors, whereas thrombin, ETA , and V-1A receptors induced stress fiber accumulation via G alpha(12) in a n EGF receptor-independent manner. Our data demonstrate that many G(q)/G(11 )-coupled receptors induce stress fiber assembly in the absence of G alpha( q) and G alpha(11) and that this involves either a G alpha(12) or a G alpha (13)/EGF receptor-mediated pathway.