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首页> 外文期刊>Molecular and Cellular Biology >A yeast mitogen-activated protein kinase homolog (Mpk1p) mediates signalling by protein kinase C.
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A yeast mitogen-activated protein kinase homolog (Mpk1p) mediates signalling by protein kinase C.

机译：酵母促有丝分裂原激活的蛋白激酶同源物（Mpk1p）介导蛋白激酶C的信号传导。

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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.
机译：丝裂素活化的蛋白（MAP）激酶通过蛋白激酶级联反应对多种刺激而被激活，从而导致其在酪氨酸和苏氨酸残基上的磷酸化。这种级联的分子性质才刚刚开始出现。在这里，我们报告的酿酒酵母基因的分离，该基因编码哺乳动物MAP激酶的功能类似物，命名为MPK1（用于MAP激酶）。分离出MPK1基因作为与BCK1基因缺失相关的细胞溶解缺陷的剂量依赖性抑制剂。还预测BCK1基因编码一种蛋白激酶，该蛋白激酶已被提议在PKC1编码的蛋白激酶C同功酶的下游起作用。 MPK1基因具有一个1.5 kb的连续阅读框，预计可编码53 kDa蛋白。预测的Mpk1蛋白（Mpk1p）与非洲爪蟾MAP激酶以及酵母交配信息素应答途径组分Fus3p和Kss1p共享48％至50％的序列同一性。 MPK1的缺失导致与温度相关的细胞裂解缺陷，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途径中起作用。非洲爪蟾MAP激酶的表达抑制了与MPK1缺失相关的缺陷，但未抑制与FUS3或KSS1缺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的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会严重损害Mpk1p的功能。额外的上位性实验以及PKC1介导的途径和信息素反应途径之间的总体结构相似性表明，Pkc1p调节蛋白激酶级联反应，其中Bck1p激活一对蛋白激酶，称为Mkk1p和Mkk2p（对于MAP激酶激酶） ，进而激活Mpk1p。

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