Cell signalling diversity of the Gqα family of heterotrimeric G proteins

• Published in: Cellular signalling 2006-02, Vol.18 (2), p.135-150
• Main Authors: Hubbard, Katherine B., Hepler, John R.
• Format: Article
• Language: English
• Subjects: G11α; G14α; G15α; G16α; GPCR; Gq family; Gqα; Heterotrimeric G proteins; Inositol lipid signalling; PLC-β; RGS proteins; RhoGEF
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2005.08.004

Many receptors for neurotransmitters and hormones rely upon members of the Gqα family of heterotrimeric G proteins to exert their actions on target cells. Gα subunits of the Gq class of G proteins (Gqα, G11α, G14α and G15/16α) directly link receptors to activation of PLC-β isoforms which, in turn, stimulate inositol lipid (i.e. calcium/PKC) signalling. Although Gqα family members share a capacity to activate PLC-β, they also differ markedly in their biochemical properties and tissue distribution which predicts functional diversity. Nevertheless, established models suggest that Gqα family members are functionally redundant and that their cellular responses are a result of PLC-β activation and downstream calcium/PKC signalling. Growing evidence, however, indicates that Gqα, G11α, G14α and G15/16α are functionally diverse and that many of their cellular actions are independent of inositol lipid signalling. Recent findings show that Gqα family members differ with regard to their linked receptors and downstream binding partners. Reported binding partners distinct from PLC-β include novel candidate effector proteins, various regulatory proteins, and a growing list of scaffolding/adaptor proteins. Downstream of these signalling proteins, Gqα 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 Gqα family members in cardiac, lung, brain and platelet functions among other physiological processes. Taken together, these findings demonstrate that Gqα, G11α, G14α and G15/16α regulate both overlapping and distinct signalling pathways, indicating that they are more functionally diverse than previously thought.