Activation of the Smk1 mitogen-activated protein kinase by developmentally regulated autophosphorylation.
Activation of the Smk1 mitogen-activated protein kinase by developmentally regulated autophosphorylation.
复制标题
通过发育调节的自磷酸化激活 Smk1 丝裂原激活蛋白激酶。
DOI：
10.1128/mcb.00973-12
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发表时间：
2013
影响因子：
5.3
通讯作者：
Winter,Edward
中科院分区：
文献类型：
--
作者：
Whinston,Elizabeth;Omerza,Gregory;Singh,Amrita;Tio,ChongWai;Winter,Edward
Smk 1是酵母中控制孢子形态发生的减数分裂特异性丝裂原活化蛋白激酶（MAPK）。与其他MAPK类似，它由其T-X-Y激活基序的双重磷酸化控制。然而，Smk 1不被原型MAPK激酶磷酸化。在这里，我们表明，T残基Smk 1的激活基序是磷酸化的细胞周期蛋白依赖性激酶（CDK）激活激酶，Cak 1。Y残基在独立的分子内反应中自磷酸化，这需要减数分裂特异性蛋白Ssp 2。虽然SMK 1和SSP 2都是减数分裂中期特异表达的基因，但Smk 1蛋白在SSP 2之前就开始积累。因此，Smk 1在孢子形成早期以低活性（pT）形式存在，在程序后期以高活性（pT/pY）形式存在。Ssp 2必须存在时，Smk 1正在产生激活自磷酸化反应，这表明Ssp 2通过Smk 1的过渡中间形式的行为。这些发现为Smk 1活性阈值是如何产生的提供了一个机制解释。他们证明了MAPK的分子内自磷酸化可以被调节，并提出了将MAPK输出与发育程序偶联的新机制。
Smk1 is a meiosis-specific mitogen-activated protein kinase (MAPK) inSaccharomyces cerevisiaethat controls spore morphogenesis. Similar to other MAPKs, it is controlled by dual phosphorylation of its T-X-Y activation motif. However, Smk1 is not phosphorylated by a prototypical MAPK kinase. Here, we show that the T residue in Smk1's activation motif is phosphorylated by the cyclin-dependent kinase (CDK)-activating kinase, Cak1. The Y residue is autophosphorylated in an independent intramolecular reaction that requires the meiosis-specific protein Ssp2. Although bothSMK1andSSP2are expressed as middle-meiosis-specific genes, Smk1 protein starts to accumulate before Ssp2. Thus, Smk1 exists in a low-activity (pT) form early in sporulation and a high-activity (pT/pY) form later in the program. Ssp2 must be present when Smk1 is being produced to activate the autophosphorylation reaction, suggesting that Ssp2 acts through a transitional intermediate form of Smk1. These findings provide a mechanistic explanation for how Smk1 activity thresholds are generated. They demonstrate that intramolecular autophosphorylation of MAPKs can be regulated and suggest new mechanisms for coupling MAPK outputs to developmental programs.