Thomas W G, Qian H, Smith N J
Molecular Endocrinology Laboratory, Baker Heart Research Institute, St Kilda Road Central, P.O. Box 6492, Melbourne 8008, Australia.
Cell Mol Life Sci. 2004 Nov;61(21):2687-94. doi: 10.1007/s00018-004-4245-2.
The type 1 angiotensin receptor (AT(1)) activates an array of intracellular signalling pathways that control cell and tissue responses to the peptide hormone angiotensin II (AngII). The capacity of AT(1) receptors to initiate and maintain such signals has typically been explained on the basis of conventional heterotrimeric guanine nucleotide binding protein (G protein) activation, specifically G(q/11). Accumulating evidence from studies utilising a variety of AT(1) receptor mutants and AngII analogues indicates that some important downstream effects of AT(1) receptors are independent of classical G protein coupling. Importantly, AT(1) receptor-mediated endocytosis, tyrosine phosphorylation signalling and mitogen-activated protein kinase activation as well as transactivation of the epidermal growth factor receptor can occur in G(q/11)-uncoupled receptor mutants. These observations point to a functional partitioning of AT(1) receptor signals that permits separation of short-term AngII actions (e.g., vasoconstriction) from more extended events, such as pathological cell growth in heart and blood vessels, and may open up new avenues for selective antagonism.
1型血管紧张素受体（AT(1)）激活一系列细胞内信号通路，这些通路控制细胞和组织对肽类激素血管紧张素II（AngII）的反应。AT(1)受体启动和维持此类信号的能力通常基于传统的异源三聚体鸟嘌呤核苷酸结合蛋白（G蛋白）激活，特别是G(q/11)来解释。利用各种AT(1)受体突变体和AngII类似物进行的研究积累的证据表明，AT(1)受体的一些重要下游效应独立于经典的G蛋白偶联。重要的是，AT(1)受体介导的内吞作用、酪氨酸磷酸化信号传导、丝裂原活化蛋白激酶激活以及表皮生长因子受体的反式激活可发生在G(q/11)未偶联的受体突变体中。这些观察结果表明AT(1)受体信号存在功能分区，这使得短期的AngII作用（如血管收缩）与更长期的事件（如心脏和血管中的病理性细胞生长）得以分离，并且可能为选择性拮抗开辟新途径。
