The role of Rho in G protein-coupled receptor signal transduction

Annu Rev Pharmacol Toxicol. 2000;40:459-89. doi: 10.1146/annurev.pharmtox.40.1.459.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • GTP-Binding Proteins / physiology*
  • Guanine Nucleotide Exchange Factors / physiology*
  • Humans
  • Phospholipids / metabolism
  • Protein-Tyrosine Kinases / physiology
  • Receptors, Cell Surface / physiology*
  • Rho Guanine Nucleotide Exchange Factors
  • Signal Transduction*
  • rhoA GTP-Binding Protein / physiology*


  • Guanine Nucleotide Exchange Factors
  • Phospholipids
  • Receptors, Cell Surface
  • Rho Guanine Nucleotide Exchange Factors
  • Protein-Tyrosine Kinases
  • GTP-Binding Proteins
  • rhoA GTP-Binding Protein