The role of Rho in G protein-coupled receptor signal transduction.
Low molecular weight G proteins of the Rho subfamily are regulators of actin cytoskeletal organization. In contrast to the heterotrimeric G proteins, the small GTPases are not directly activated through ligand binding to G protein-coupled receptors (GPCRs). However, a subset of GPCRs, including those for lysophosphatidic acid and thrombin, induce stress fibers, focal adhesions, and cell rounding through Rho-dependent pathways. C3 exoenzyme has been a useful tool for demonstrating Rho involvement in these and other responses, including Ca2+ sensitization of smooth muscle contraction, cell migration, transformation, and serum response element-mediated gene expression. Most of the GPCRs that induce Rho-dependent responses can activate Gq, but this is not a sufficient signal. Recent data demonstrate that G alpha 12/13 can induce Rho-dependent responses. Furthermore, G alpha 12/13 can bind and activate Rho-specific guanine nucleotide exchange factors, providing a mechanism by which GPCRs that couple to G alpha 12/13 could activate Rho and its downstream responses.
Sah
V P
VP
Department of Pharmacology, University of California, San Diego 92093-0636, USA. vtansah@ucsd.edu
Seasholtz
T M
TM
Sagi
S A
SA
Brown
J H
JH
D000818:Animals; D019204:GTP-Binding Proteins / Q000502:physiology*; D020662:Guanine Nucleotide Exchange Factors / Q000502:physiology*; D006801:Humans; D010743:Phospholipids / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology*; D064067:Rho Guanine Nucleotide Exchange Factors; D015398:Signal Transduction; D020742:rhoA GTP-Binding Protein / Q000502:physiology*
D020662:Guanine Nucleotide Exchange Factors; D010743:Phospholipids; D011956:Receptors, Cell Surface; D064067:Rho Guanine Nucleotide Exchange Factors; D011505:Protein-Tyrosine Kinases; D019204:GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein