G protein-coupled receptor signalling and cross-talk: achieving rapidity and specificity.
Activation of a given type of G protein-coupled receptor (GPCR) triggers a limited set of signalling events in a very rapid and specific manner. The classical paradigm of GPCR signalling was rather linear and sequential. Emerging evidence, however, has revealed that this is only a part of the complex signalling mediated by GPCR. Propagation of GPCR signalling involves cross-regulation of many but specific pathways, including cross-talks between different GPCRs as well as with other signalling pathways. Moreover, it is increasingly apparent that GPCRs can activate both heterotrimeric G protein-dependent and G protein-independent signalling pathways. In this review, we discuss how the signallings initiated by GPCRs achieve rapidity as well as specificity, and how the GPCRs can cross-regulate other specific signalling pathways at the same time. New concepts regarding GPCR signalling have been arising to address this issue, which include multiprotein signalling complex and signalling compartment in microdomain concepts that enable close colocalization or even contact among the proteins engaged in the specific signal transduction. The final outcome of a stimulation of GPCR will thus be the sum of its own specific set of intracellular signalling pathways it regulates.
Hur
Eun Mi
EM
Department of Life Science, Division of Molecular and Life Sciences, Pohang University of Science and Technology, San 31, Hyoja Dong, 790-784, Pohang, South Korea.
Kim
Kyong Tai
KT
D000818:Animals; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism; D007700:Kinetics; D046911:Macromolecular Substances; D008954:Models, Biological; D046912:Multiprotein Complexes; D020239:Receptor Cross-Talk; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction
D007473:Ion Channels; D046911:Macromolecular Substances; D046912:Multiprotein Complexes; D011956:Receptors, Cell Surface; D020962:Heterotrimeric GTP-Binding Proteins