Abstract
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 Gq/G11-coupled receptors. Using fibroblast
cell lines derived from wild-type and Galphaq/Galpha11-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 V1A, endothelin ETA, and serotonin
5-HT2C receptors induced stress fiber formation in either the presence
or absence of Galphaq/Galpha11. Stress fiber assembly induced through
the muscarinic M1 and the metabotropic glutamate subtype 1alpha receptors
was dependent on Gq/G11 proteins. The activation of the Gq/G11-coupled
endothelin ETB and angiotensin AT1A receptors failed to induce stress
fiber formation. Lysophosphatidic acid, B2, and 5-HT2C receptor-mediated
stress fiber formation was dependent on Galpha13 and involved epidermal
growth factor (EGF) receptors, whereas thrombin, ETA, and V1A receptors
induced stress fiber accumulation via Galpha12 in an EGF receptor-independent
manner. Our data demonstrate that many Gq/G11-coupled receptors induce
stress fiber assembly in the absence of Galphaq and Galpha11 and
that this involves either a Galpha12 or a Galpha13/EGF receptor-mediated
pathway.
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