Cell signalling diversity of the Gqα family of heterotrimeric G proteins

Many receptors for neurotransmitters and hormones rely upon members of the Gq alpha family of heterotrimeric G proteins to exert their actions on target cells. G alpha subunits of the Gq class of G proteins (Gq alpha, G11 alpha, G14 alpha and G 15/16 alpha) directly link receptors to activation of PLC-beta isofornis which, in turn, stimulate inositol lipid (i.e. calcium/PKC) signalling. Although Gq alpha family members share a capacity to activate PLC-beta they also differ markedly in their biochemical properties and tissue distribution which predicts functional diversity. Nevertheless, established models suggest that Gq alpha family members are functionally redundant and that their cellular responses are a result of PLC-beta activation and downstream calcium/PKC signalling. Growing evidence, however, indicates that Gq alpha, G11 alpha, G14 alpha and G 15/16 alpha are functionally diverse and that many of their cellular actions are independent of inositol lipid signalling. Recent findings show that Gqa family members differ with regard to their linked receptors and downstream binding partners. Reported binding partners distinct from PLC-beta include novel candidate effector proteins, various regulatory proteins, and a growing list of scaffolding/adaptor proteins. Downstream of these signalling proteins, Gq alpha family members exhibit unexpected differences in the signalling pathways and the gene expression profiles they regulate. Finally, genetic studies using whole animal models demonstrate the importance of certain Gq alpha family members in cardiac, lung, brain and platelet functions among other physiological processes. Taken together, these findings demonstrate that Gq alpha, G11 alpha, G14 alpha and G15/16 alpha regulate both overlapping and distinct signalling pathways, indicating that they are more functionally diverse than previously thought. (c) 2005 Elsevier Inc. All rights reserved.