Heterotrimeric G Protein Signaling Outside the Realm of Seven Transmembrane Domain Receptors

摘要

Heterotrimeric G proteins, consisting of the guanine nucleotide-binding Gα subunits with GTPase activity and the closely associated Gβ and Gγ subunits, are important signaling components for receptors with seven transmembrane domains (7TMRs). These receptors, also termed G protein-coupled receptors (GPCRs), act as guanine nucleotide exchange factors upon agonist stimulation. There is now accumulating evidence for noncanonical functions of heterotrimeric G proteins independent of 7TMR coupling. Gα proteins belonging to all 4 subfamilies, including Gs, Gi, Gq, and G12 are found to play important roles in receptor tyrosine kinase signaling, regulation of oxidant production, development, and cell migration, through physical and functional interaction with proteins other than 7TMRs. Association of Gα with non-7TMR proteins also facilitates presentation of these G proteins to specific cellular microdomains. This Minireview aims to summarize our current understanding of the noncanonical roles of Gα proteins in cell signaling and to discuss unresolved issues including regulation of Gα activation by proteins other than the 7TMRs.