G protein specificity: traffic direction required

Cell Signal. 2002 May;14(5):407-18. doi: 10.1016/s0898-6568(01)00259-5.


This review focuses on the coupling specificity of the Galpha and Gbetagamma subunits of pertussis toxin (PTX)-sensitive G(i/o) proteins that mediate diverse signaling pathways, including regulation of ion channels and other effectors. Several lines of evidence indicate that specific combinations of G protein alpha, beta and gamma subunits are required for different receptors or receptor-effector networks, and that a higher degree of specificity for Galpha and Gbetagamma is observed in intact systems than reported in vitro. The structural determinants of receptor-G protein specificity remain incompletely understood, and involve receptor-G protein interaction domains, and perhaps other scaffolding processes. By identifying G protein specificity for individual receptor signaling pathways, ligands targeted to disrupt individual pathways of a given receptor could be developed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenylyl Cyclases / metabolism
  • Amino Acid Sequence
  • Animals
  • Calcium Channels / metabolism
  • GTP-Binding Protein alpha Subunits, Gi-Go / chemistry
  • GTP-Binding Protein alpha Subunits, Gi-Go / physiology*
  • GTP-Binding Protein beta Subunits*
  • GTP-Binding Protein gamma Subunits*
  • Heterotrimeric GTP-Binding Proteins / chemistry
  • Heterotrimeric GTP-Binding Proteins / metabolism
  • Heterotrimeric GTP-Binding Proteins / physiology*
  • Humans
  • Macromolecular Substances
  • Models, Biological
  • Potassium Channels / metabolism
  • Receptors, Cell Surface / metabolism
  • Sequence Alignment
  • Signal Transduction*


  • Calcium Channels
  • G-protein Beta gamma
  • GTP-Binding Protein beta Subunits
  • GTP-Binding Protein gamma Subunits
  • Macromolecular Substances
  • Potassium Channels
  • Receptors, Cell Surface
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • Heterotrimeric GTP-Binding Proteins
  • Adenylyl Cyclases