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 invokes 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 actuate both heterotrimeric G protein-dependent and G protein-independent signalling pathways. In this review, we discuss how the signalling; 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 ill microdomain concepts that enable close colocalization or even contact among the proteins engaged in the specific signal transduction. The filial outcome of a stimulation of GPCR will thus be the sum of its own specific set of intracellular signalling pathways it regulates. (C) 2002 Elsevier Science Inc. All rights reserved.