Decoding Gα_q signaling

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• 作者：Irene Litosch ^{ilitosch@med.miami.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Diacylglycerol kinase ; Effectors ; Gαq ; G protein-coupled receptor ; GTPase activating protein ; Phosphatidic acid ; Phosphatidylinositol-4 ; 5 bisphosphate ; Phospholipase C-β ; Phospholipase C-ε ; Protein kinase C ; p63RhoGEF ; G protein regulated kinase 2 ; Phosphatidylinositol-3 kinase ; Protein kinase C ; Tetratricopeptide repeat 1 ; Transient receptor potential cation channel 8
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：1 May 2016
• 年：2016
• 卷：152
• 期：Complete
• 页码：99-106
• 全文大小：703 K

文摘

Gα_q signals with phospholipase C-β (PLC-β) to modify behavior in response to an agonist-bound GPCR. While the fundamental steps which prime Gα_q to interact with PLC-β have been identified, questions remain concerning signal strength with PLC-β and other effectors. Gα_q is generally viewed to function as a simple ON and OFF switch for its effector, dependent on the binding of GTP or GDP. However, Gα_q does not have a single effector, Gα_q has many different effectors. Furthermore, select effectors also regulate Gα_q activity. PLC-β is a lipase and a GTPase activating protein (GAP) selective for Gα_q. The contribution of G protein regulating activity to signal amplitude remains unclear. The unique PLC-β coiled-coil domain is essential for maximum Gα_q response, both lipase and GAP. Nonetheless, coiled-coil domain associations necessary to maximum response have not been revealed by the structural approach. This review discusses progress towards understanding the basis for signal strength with PLC-β and other effectors. Shared and effector-specific interactions have been identified. Finally, the evidence for allosteric regulation of lipase stimulation by protein kinase C, the membrane, phosphatidic acid, phosphatidylinositol-4, 5-bisphosphate and GPCR is explored. Endogenous allosteric regulators can suppress or enhance maximum lipase stimulation dependent on the PLC-β coiled-coil domain. A better understanding of allosteric modulation may therefore identify a wealth of new targets to regulate signal strength and behavior.