Structure and function of heterotrimeric G protein-regulated Rho guanine nucleotide exchange factors

Mol Pharmacol. 2010 Feb;77(2):111-25. doi: 10.1124/mol.109.061234. Epub 2009 Oct 30.

Abstract

Activation of certain classes of G protein-coupled receptors (GPCRs) can lead to alterations in the actin cytoskeleton, gene transcription, cell transformation, and other processes that are known to be regulated by Rho family small-molecular-weight GTPases. Although these responses can occur indirectly via cross-talk from canonical heterotrimeric G protein cascades, it has recently been demonstrated that Dbl family Rho guanine nucleotide exchange factors (RhoGEFs) can serve as the direct downstream effectors of heterotrimeric G proteins. Heterotrimeric Galpha(12/13), Galpha(q), and Gbetagamma subunits are each now known to directly bind and regulate RhoGEFs. Atomic structures have recently been determined for several of these RhoGEFs and their G protein complexes, providing fresh insight into the molecular mechanisms of signal transduction between GPCRs and small molecular weight G proteins. This review covers what is currently known about the structure, function, and regulation of these recently recognized effectors of heterotrimeric G proteins.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Guanine Nucleotide Exchange Factors / chemistry*
  • Guanine Nucleotide Exchange Factors / metabolism
  • Guanine Nucleotide Exchange Factors / physiology*
  • Heterotrimeric GTP-Binding Proteins / chemistry*
  • Heterotrimeric GTP-Binding Proteins / metabolism*
  • Heterotrimeric GTP-Binding Proteins / physiology
  • Humans
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, G-Protein-Coupled / physiology
  • Rho Guanine Nucleotide Exchange Factors
  • Signal Transduction / physiology

Substances

  • Guanine Nucleotide Exchange Factors
  • Receptors, G-Protein-Coupled
  • Rho Guanine Nucleotide Exchange Factors
  • Heterotrimeric GTP-Binding Proteins