Interaction of a G-protein β-subunit with a conserved sequence in Ste20/PAK family protein kinases
Interaction of a G-protein β-subunit with a conserved sequence in Ste20/PAK family protein kinases
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DOI：
10.1038/34448
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发表时间：
1998-01-08
期刊：
影响因子：
64.8
通讯作者：
Leberer, E
中科院分区：
文献类型：
--
作者：
Leeuw, T;Wu, CL;Leberer, E
Ste 20/PAK家族的丝氨酸/苏氨酸蛋白激酶参与了从异源三聚体G蛋白到丝裂原活化蛋白（MAP）激酶级联的信号传导（1，2）。在酿酒酵母中，Ste 20参与将交配信息素信号从异源三聚体G蛋白的β γ亚基（分别由STE 4和STE 18基因编码）传递到下游MAP激酶级联（1）。我们已经确定了一个结合位点的G-蛋白β亚基（G β）的非催化羧基末端区域的Ste 20及其哺乳动物同源物，p21激活的蛋白激酶（PAKs）。G β与Ste 20中该位点的结合受信息素与受体结合的调节。阻止这种关联的G β和Ste 20突变阻断了MAP激酶级联的激活。考虑到Ste 20/PAK家族成员和G蛋白亚基的高度结构和功能保守性，我们的研究结果为这些激酶在从酵母到哺乳动物的生物体中G β γ介导的信号转导中的作用提供了一个可能的模型。
Serine/threonine protein kinases of the Ste20/PAK family have been implicated in the signalling from heterotrimeric G proteins to mitogen-activated protein (MAP) kinase cascades(1,2). in the yeast Saccharomyces cerevisiae, Ste20 is involved in transmitting the mating-pheromone signal from the beta gamma-subunits (encoded by the STE4 and STE18 genes, respectively) of a heterotrimeric G protein to a downstream MAP kinase cascade(1). We have identified a binding site for the G-protein beta-subunit (G beta) in the non-catalytic carboxy-terminal regions of Ste20 and its mammalian homologues, the p21-activated protein kinases (PAKs). Association of G beta with this site in Ste20 was regulated by binding of pheromone to the receptor. Mutations in G beta and Ste20 that prevented this association blocked activation of the MAP kinase cascade. Considering the high degree of structural and functional conservation of Ste20/PAK family members and G-protein subunits, our results provide a possible model for a role of these kinases in G beta gamma-mediated signal transduction in organisms ranging from yeast to mammals.