The ubiquitously expressed heterotrimeric guanine nucleotide-binding proteins (G-proteins) G12 and G13 have been shown to activate the small GTPase Rho. Rho stimulation leads to a rapid remodeling of the actin cytoskeleton and subsequent stress fiber formation. We investigated the involvement of G12 or G13 in stress fiber formation induced through a variety of G(q)/G11-coupled receptors. Using fibroblast cell lines derived from wild-type and Gα(q)/Gα11-deficient mice, we show that agonist- dependent activation of the endogenous receptors for thrombin or lysophosphatidic acid and of the heterologously expressed bradykinin B2, vasopressin V(1A), endothelin ET(A), and serotonin 5-HT(2C) receptors induced stress fiber formation in either the presence or absence of Gα(q)/Gα11. Stress fiber assembly induced through the muscarinic M1 and the metabotropic glutamate subtype 1α receptors was dependent on G(q)/G11 proteins. The activation of the G(q)/G11-coupled endothelin ET(B) and angiotensin AT(1A) receptors failed to induce stress fiber formation. Lysophosphatidic acid, B2, and 5-HT(2C) receptor-mediated stress fiber formation was dependent on Gα13 and involved epidermal growth factor (EGF) receptors, whereas thrombin, ET(A), and V(1A) receptors induced stress fiber accumulation via Gα12 in an EGF receptorin-dependent manner. Our data demonstrate that many G(q)/G11-coupled receptors induce stress fiber assembly in the absence of Gα(q) and Gα11 and that this involves either a Gα12 or a Gα13/EGF receptor-mediated pathway.
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