The protein kinase Mos is responsible for the activation of MEK1 and p42 mitogen-activated protein kinase during Xenopus oocyte maturation and during mitosis in Xenopus egg extracts. Here we show that the activation of Mos depends upon the phosphorylation of Ser 3, a residue previously implicated in the regulation of Mos stability; the dephosphorylation of Ser 105, a previously unidentified phosphorylation site conserved in Mos proteins; and the regulated dissociation of Mos from CK2β. Mutation of Ser 3 to alanine and/or mutation of Ser 105 to glutamate produces a Mos protein that is defective for M-phase activation, as assessed by in vitro kinase assays, and defective for induction of oocyte maturation and maintenance of the spindle assembly checkpoint in extracts. Interestingly, Ser 105 is situated at the beginning of helix αC in the N-terminal lobe of the Mos kinase domain. Changes in the orientation of this helix have been previously implicated in the activation of Cdk2 and Src family tyrosine kinases. Our work suggests that Ser 105 dephosphorylation represents a novel mechanism for reorienting helix αC.
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机译：蛋白激酶Mos负责在非洲爪蟾卵母细胞成熟过程中以及非洲爪蟾卵提取物中的有丝分裂过程中激活MEK1和p42丝裂原活化的蛋白激酶。在这里，我们显示Mos的激活取决于Ser 3的磷酸化，Ser 3是先前参与Mos稳定性调节的一个残基。 Ser 105的去磷酸化，Ser 105是一个以前未知的在Mos蛋白中保守的磷酸化位点;以及Mos与CK2β的受控解离。 Ser 3突变为丙氨酸和/或Ser 105突变为谷氨酸可产生Mos蛋白，该蛋白通过体外激酶测定评估为M相激活有缺陷，而对诱导卵母细胞成熟和维持纺锤体检查点有缺陷在提取物中。有趣的是，Ser 105位于Mos激酶结构域N末端叶的螺旋αC的起点。该螺旋的方向变化先前已与Cdk2和Src家族酪氨酸激酶的激活有关。我们的工作表明，Ser 105的去磷酸化代表了一种重新定位螺旋αC的新机制。
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