MITOGEN-ACTIVATED PROTEIN-KINASES PHOSPHORYLATE NUCLEAR LAMINS AND DISPLAY SEQUENCE SPECIFICITY OVERLAPPING THAT OF MITOTIC PROTEIN KINASE-P34CDC2
MITOGEN-ACTIVATED PROTEIN-KINASES PHOSPHORYLATE NUCLEAR LAMINS AND DISPLAY SEQUENCE SPECIFICITY OVERLAPPING THAT OF MITOTIC PROTEIN KINASE-P34CDC2
复制标题
DOI：
10.1111/j.1432-1033.1992.tb16779.x
复制
发表时间：
1992-04-01
期刊：
影响因子：
--
通讯作者：
NIGG, EA
中科院分区：
文献类型：
--
作者：
PETER, M;SANGHERA, JS;NIGG, EA
丝裂原活化蛋白（MAP）激酶家族成员参与介导细胞进入细胞周期以及通过减数分裂M期。 这些激酶引起了人们极大的兴趣，因为它们的激活涉及酪氨酸和苏氨酸残基的磷酸化，但对它们的生理靶点知之甚少。 在这项研究中，两个不同的成员的MAP激酶家族（p44mpk和p42mapk）被证明磷酸化鸡核纤层蛋白B2在一个单一的网站确定为Ser16。 此外，这些MAP激酶引起体外组装的纵向核纤层蛋白头-尾聚合物的解聚。 Ser16在体内有丝分裂过程中被磷酸化，并在体外成为有丝分裂蛋白激酶p34cdc2的靶点。 因此，提出核纤层蛋白是p34cdc2的直接体内底物。 定量分析表明，核纤层蛋白B2，在体外测定时，这一建议是一个更好的底物p34cdc2比MAP激酶。 然而，不排除MAP激酶在核纤层蛋白磷酸化中的生理作用。 MAP激酶家族的成员显示与p34cdc2重叠的序列特异性的观察结果提出了这样的可能性，即p34cdc2的一些假定底物实际上可能是MAP激酶的生理底物。
Members of the mitogen-activated protein (MAP) kinase family are implicated in mediating entry of cells into the cell cycle, as well as passage through meiotic M phase. These kinases have attracted much interest because their activation involves phosphorylation on both tyrosine and threonine residues, but little is known about their physiological targets. In this study, two distinct members of the MAP kinase family (p44mpk and p42mapk) are shown to phosphorylate chicken lamin B2 at a single site identified as Ser16. Moreover, these MAP kinases cause depolymerization of in-vitro-assembled longitudinal lamin head-to-tail polymers. Ser16 was previously shown to be phosphorylated during mitosis in vivo, and to be a target of the mitotic protein kinase p34cdc2 in vitro. Accordingly, lamins were proposed to be direct in vivo substrates of p34cdc2. This proposal is supported by quantitative analyses indicating that lamin B2, when assayed in vitro, is a substantially better substrate for p34cdc2 than for MAP kinases. Nevertheless, a physiological role of MAP kinases in lamin phosphorylation is not excluded. The observation that members of the MAP kinase family display sequence specificities overlapping that of p34cdc2 raises the possibility that some of the purported substrates of p34cdc2 may actually be physiological substrates of MAP kinases.