Cismowski M J, Takesono A, Bernard M L, Duzic E, Lanier S M
Department of Pharmacology, Medical University of South Carolina, Charleston 29425, USA.
Life Sci. 2001 Apr 6;68(19-20):2301-8. doi: 10.1016/s0024-3205(01)01019-0.
Heterotrimeric G-protein signalling systems are primarily activated via cell surface receptors possessing the seven membrane span motif. Several observations suggest the existence of other modes of input to such signalling systems either downstream of effectors or at the level of G-proteins themselves. Using a functional screen based upon the pheromone response pathway in Saccharomyces cerevisiae, we identified three proteins, AGS1-3 (for Activators of G-protein Signalling), that activated heterotrimeric G-protein signalling pathways in the absence of a typical receptor. AGS1 defines a distinct member of the super family of ras related proteins. AGS2 is identical to mouse Tctex1, a protein that exists as a light chain component of the cytoplasmic motor protein dynein and subserves as yet undefined functions in cell signalling pathways. AGS3 possesses a series of tetratrico repeat motifs and a series of four amino acid repeats termed G-protein regulatory motifs. The GPR motifs are found in a number of proteins that interact with and regulate Galpha. Although each AGS protein activates G-protein signaling, they do so by different mechanisms within the context of the G-protein activation/deactivation cycle. AGS proteins provide unexpected mechanisms for input to heterotrimeric G-protein signalling pathways.
异源三聚体G蛋白信号系统主要通过具有七跨膜基序的细胞表面受体激活。一些观察结果表明，在效应器下游或G蛋白本身水平上，存在其他输入到此类信号系统的模式。利用基于酿酒酵母中信息素反应途径的功能筛选，我们鉴定出三种蛋白，AGS1 - 3（G蛋白信号激活剂），它们在没有典型受体的情况下激活异源三聚体G蛋白信号通路。AGS1定义了ras相关蛋白超家族的一个独特成员。AGS2与小鼠Tctex1相同，Tctex1是一种作为细胞质运动蛋白动力蛋白轻链成分存在的蛋白，在细胞信号通路中发挥尚未明确的功能。AGS3具有一系列四三肽重复基序和一系列称为G蛋白调节基序的四氨基酸重复序列。GPR基序存在于许多与Gα相互作用并调节Gα的蛋白质中。尽管每种AGS蛋白都激活G蛋白信号，但它们在G蛋白激活/失活循环的背景下通过不同机制实现。AGS蛋白为异源三聚体G蛋白信号通路的输入提供了意想不到的机制。
