G protein specificity: Traffic direction required

This review focuses on the coupling specificity of the Galpha and Gbetagamma subunits of pertussis toxin (PTX)-sensitive Galpha 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 arc 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. (C) 2002 Elsevier Science Inc. All rights reserved.