Cell signalling diversity of the Gqalpha family of heterotrimeric G proteins.
Cell signalling diversity of the Gqalpha family of heterotrimeric G proteins.
复制标题
DOI：
--
复制
发表时间：
2006
影响因子：
4.8
通讯作者：
Katherine B. Hubbard;J. Hepler
中科院分区：
文献类型：
--
作者：
Katherine B. Hubbard;J. Hepler
许多神经递质和激素受体依赖于异三聚体 G 蛋白 Gqalpha 家族的成员来对靶细胞发挥作用。 Gq 类 G 蛋白（Gqalpha、G11alpha、G14alpha 和 G15/16alpha）的 Galpha 亚基直接将受体与 PLC-β 同种型的激活连接起来，从而刺激肌醇脂质（即钙/PKC）信号传导。尽管 Gqalpha 家族成员都有激活 PLC-beta 的能力，但它们在生化特性和组织分布方面也存在显着差异，这预示着功能多样性。然而，已建立的模型表明 Gqalpha 家族成员在功能上是冗余的，它们的细胞反应是 PLC-β 激活和下游钙/PKC 信号传导的结果。然而，越来越多的证据表明，Gqalpha、G11alpha、G14alpha 和 G15/16alpha 具有不同的功能，并且它们的许多细胞作用独立于肌醇脂质信号传导。最近的研究结果表明，Gqalpha 家族成员在连接的受体和下游结合配偶体方面有所不同。报道的与 PLC-beta 不同的结合配偶体包括新型候选效应蛋白、各种调节蛋白以及越来越多的支架/适配器蛋白。这些信号蛋白的下游，Gqalpha 家族成员在信号通路及其调节的基因表达谱方面表现出意想不到的差异。最后，使用整体动物模型的遗传学研究证明了某些 Gqalpha 家族成员在心脏、肺、大脑和血小板功能以及其他生理过程中的重要性。总而言之，这些发现表明 Gqalpha、G11alpha、G14alpha 和 G15/16alpha 调节重叠和不同的信号通路，表明它们在功能上比之前认为的更加多样化。
Many receptors for neurotransmitters and hormones rely upon members of the Gqalpha family of heterotrimeric G proteins to exert their actions on target cells. Galpha subunits of the Gq class of G proteins (Gqalpha, G11alpha, G14alpha and G15/16alpha) directly link receptors to activation of PLC-beta isoforms which, in turn, stimulate inositol lipid (i.e. calcium/PKC) signalling. Although Gqalpha 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 Gqalpha 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 Gqalpha, G11alpha, G14alpha and G15/16alpha are functionally diverse and that many of their cellular actions are independent of inositol lipid signalling. Recent findings show that Gqalpha 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, Gqalpha 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 Gqalpha family members in cardiac, lung, brain and platelet functions among other physiological processes. Taken together, these findings demonstrate that Gqalpha, G11alpha, G14alpha and G15/16alpha regulate both overlapping and distinct signalling pathways, indicating that they are more functionally diverse than previously thought.