A YEAST MITOGEN-ACTIVATED PROTEIN-KINASE HOMOLOG (MPK1P) MEDIATES SIGNALING BY PROTEIN-KINASE-C
A YEAST MITOGEN-ACTIVATED PROTEIN-KINASE HOMOLOG (MPK1P) MEDIATES SIGNALING BY PROTEIN-KINASE-C
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DOI：
10.1128/mcb.13.5.3067
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发表时间：
1993-05-01
影响因子：
5.3
通讯作者：
LEVIN, DE
中科院分区：
文献类型：
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作者：
LEE, KS;IRIE, K;LEVIN, DE
丝裂原激活蛋白 (MAP) 激酶通过蛋白激酶级联响应各种刺激而被激活，导致其酪氨酸和苏氨酸残基磷酸化。这种级联的分子性质才刚刚开始显现。在这里，我们报告了编码哺乳动物 MAP 激酶功能类似物的酿酒酵母基因的分离，称为 MPK1（MAP 激酶）。 MPK1 基因被分离为与 BCK1 基因缺失相关的细胞裂解缺陷的剂量依赖性抑制因子。 BCK1 基因还被预测编码一种蛋白激酶，该蛋白激酶被认为在 PKC1 编码的蛋白激酶 C 同工酶的下游发挥作用。 MPK1 基因拥有一个 1.5 kb 不间断的开放阅读框，预计可编码 53 kDa 蛋白质。预测的 Mpk1 蛋白 (Mpk1p) 与非洲爪蟾 MAP 激酶以及酵母交配信息素响应途径组件 Fus3p 和 Kss1p 具有 48% 至 50% 的序列同一性。 MPK1 的缺失导致了温度依赖性细胞裂解缺陷，这与 BCK1 缺失导致的细胞裂解缺陷几乎没有区别，这表明这些基因编码的蛋白激酶在共同的途径中发挥作用。爪蟾 MAP 激酶的表达抑制了与 MPK1 丢失相关的缺陷，但没有抑制与 FUS3 或 KSS1 丢失相关的交配相关缺陷，表明前两种蛋白激酶之间的功能保守。 Mpk1p 假定的磷酸化酪氨酸和苏氨酸残基分别突变为苯丙氨酸和丙氨酸，严重损害了 Mpk1p 的功能。其他上位性实验以及 PKC1 介导的通路和信息素响应通路之间的总体结构相似性表明，Pkc1p 调节蛋白激酶级联，其中 Bck1p 激活一对蛋白激酶，称为 Mkk1p 和 Mkk2p（MAP 激酶激酶），进而激活 Mpk1p。
Mitogen-activated protein (MAP) kinases are activated in response to a variety of stimuli through a protein kinase cascade that results in their phosphorylation on tyrosine and threonine residues. The molecular nature of this cascade is just beginning to emerge. Here we report the isolation of a Saccharomyces cerevisiae gene encoding a functional analog of mammalian MAP kinases, designated MPK1 (for MAP kinase). The MPK1 gene was isolated as a dosage-dependent suppressor of the cell lysis defect associated with deletion of the BCK1 gene. The BCK1 gene is also predicted to encode a protein kinase which has been proposed to function downstream of the protein kinase C isozyme encoded by PKC1. The MPK1 gene possesses a 1.5-kb uninterrupted open reading frame predicted to encode a 53-kDa protein. The predicted Mpk1 protein (Mpk1p) shares 48 to 50% sequence identity with Xenopus MAP kinase and with the yeast mating pheromone response pathway components, Fus3p and Kss1p. Deletion of MPK1 resulted in a temperature-dependent cell lysis defect that was virtually indistinguishable from that resulting from deletion of BCK1, suggesting that the protein kinases encoded by these genes function in a common pathway. Expression of Xenopus MAP kinase suppressed the defect associated with loss of MPK1 but not the mating-related defects associated with loss of FUS3 or KSS1, indicating functional conservation between the former two protein kinases. Mutation of the presumptive phosphorylated tyrosine and threonine residues of Mpk1p individually to phenylalanine and alanine, respectively, severely impaired Mpk1p function. Additional epistasis experiments, and the overall architectural similarity between the PKC1-mediated pathway and the pheromone response pathway, suggest that Pkc1p regulates a protein kinase cascade in which Bck1p activates a pair of protein kinases, designated Mkk1p and Mkk2p (for MAP kinase-kinase), which in turn activate Mpk1p.