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题目:: RGS14 regulates the lifetime of G-GTP signaling but does not prolong G signaling following receptor activation in live cells.
作者:: Brown(Nicole E),Lambert(Nevin A),Hepler(John R)
状态:: 发布时间2016-10-07 , 更新时间 2016-11-16
期刊:: Pharmacol Res Perspect
摘要:: RGS14 is a multifunctional scaffolding protein possessing two distinct G protein interaction sites including a regulator of G protein signaling (RGS) domain that acts as a GTPase activating protein (GAP) to deactivate Gi/o-GTP proteins, and a G protein regulatory (GPR) motif that binds inactive Gi1/3-GDP proteins independent of G. GPR interactions with Gi recruit RGS14 to the plasma membrane to interact with Gi-linked GPCRs and regulate Gi signaling. While RGS14 actions on G proteins are well characterized, consequent effects on G signaling remain unknown. Conventional RGS proteins act as dedicated GAPs to deactivate G and G signaling following receptor activation. RGS14 may do the same or, alternatively, may coordinate its actions to deactivate G-GTP with the RGS domain and then capture the same G-GDP via its GPR motif to prevent heterotrimer reassociation and prolong G signaling. To test this idea, we compared the regulation of G protein activation and deactivation kinetics by a conventional RGS protein, RGS4, and RGS14 in response to GPCR agonist/antagonist treatment utilizing bioluminescence resonance energy transfer (BRET). Co-expression of either RGS4 or RGS14 inhibited the release of free G after agonist stimulation and increased the deactivation rate of G, consistent with their roles as GTPase activating proteins (GAPs). Overexpression of inactive Gi1 to recruit RGS14 to the plasma membrane did not alter RGS14's capacity to act as a GAP for a second Go protein. These results demonstrate the role of RGS14 as a dedicated GAP and suggest that the G protein regulatory (GPR) motif functions independently of the RGS domain and is silent in regulating GAP activity in a cellular context.
语言:: eng
DOI:

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