Pin1 acts catalytically to promote a conformational change in Cdc25
Pin1 acts catalytically to promote a conformational change in Cdc25
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DOI：
10.1016/s1097-2765(01)00245-3
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发表时间：
2001-05-01
期刊：
影响因子：
16
通讯作者：
Kirschner, MW
中科院分区：
文献类型：
--
作者：
Stukenberg, PT;Kirschner, MW
Pin1是一种必需的蛋白质，它能使小分子磷酸肽发生肽基-Pro-异构化反应。已有研究表明，Pin1通过催化关键蛋白质底物上脯氨酸的顺式/反式异构化反应来调节有丝分裂的进入。我们发现Pin1催化有丝分裂磷酸酶CDC25的构象变化，通过有限的蛋白酶消化，对磷酸丝氨酸导向的单抗(MPM-2)的差异反应，以及CDC25酶活性的变化来检测。在化学计量比小于0.0005的情况下，Pin1催化修饰CDC25的构象，并且在Pro异构酶结构域中Pin1的突变体是无效的。我们认为，尽管很难检测到，但由Pro异构化介导的磷酸化依赖的构象变化可能在细胞周期中发挥重要的调节作用。
Pin1 is an essential protein that can peptidyl-prolyl-isomerize small phosphopeptides. It has been suggested that Pin1 regulates entry into mitosis by catalyzing the cis/trans-isomerization of prolines on critical protein substrates in response to phosphorylation. We show that Pin1 catalytically generates a conformational change on the mitotic phosphatase Cdc25, as assayed by limited protease digestion, differential reactivity to a phosphoserine-proline-directed monoclonal antibody (MPM-2), and by changes in Cdc25 enzymatic activity. Pin1 catalytically modifies the conformation of Cdc25 at stoichiometries less than 0.0005, and mutants of Pin1 in the prolyl isomerase domain are not active. We suggest that, although difficult to detect, phosphorylation-dependent conformational changes mediated by prolyl isomerization may play an important regulatory role in the cell cycle.