Pin1-dependent prolyl isomerization regulates dephosphorylation of Cdc25C and tau proteins.
Pin1-dependent prolyl isomerization regulates dephosphorylation of Cdc25C and tau proteins.
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DOI：
10.1016/s1097-2765(05)00083-3
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发表时间：
2000-10
期刊：
影响因子：
16
通讯作者：
X. Zhou;O. Kops;A. Werner;P. Lu;Minhui Shen;G. Stoller;Gerhard Küllertz;M. Stark;G. Fischer-G.
中科院分区：
文献类型：
--
作者：
X. Zhou;O. Kops;A. Werner;P. Lu;Minhui Shen;G. Stoller;Gerhard Küllertz;M. Stark;G. Fischer-G.
脯氨酸之前的丝氨酸或苏氨酸残基 (pSer/Thr-Pro) 上的可逆蛋白质磷酸化是控制各种细胞过程（包括细胞分裂）的关键信号传导机制。肽中的 pSer/Thr-Pro 部分存在两种完全不同的顺式和反式构象，其转化由必需的脯氨酰异构酶 Pin1 特异性催化。先前的结果表明 Pin1 可能调节其底物的构象和去磷酸化。然而，尚不清楚磷酸化依赖性脯氨酰异构化是否发生在天然蛋白质中和/或影响 pSer/Thr-Pro 基序的去磷酸化。在这里，我们证明主要的 Pro 定向磷酸酶 PP2A 具有构象特异性，并且仅有效地使 transpSer/Thr-Pro 异构体去磷酸化。此外，Pin1 催化 Cdc25C 和 tau 中特定 pSer/Thr-Pro 基序的脯氨酰异构化，以促进 PP2A 对其进行去磷酸化。此外，Pin1 和 PP2A 显示出相互的遗传相互作用，Pin1 的脯氨酰异构酶活性对于体内细胞分裂至关重要。因此，Pin1 催化的磷酸化特异性脯氨酰异构化是调节某些 pSer/Thr-Pro 基序去磷酸化所必需的新机制。
The reversible protein phosphorylation on serine or threonine residues that precede proline (pSer/Thr-Pro) is a key signaling mechanism for the control of various cellular processes, including cell division. The pSer/Thr-Pro moiety in peptides exists in the two completely distinctcisandtransconformations whose conversion is catalyzed specifically by the essential prolyl isomerase Pin1. Previous results suggest that Pin1 might regulate the conformation and dephosphorylation of its substrates. However, it is not known whether phosphorylation-dependent prolyl isomerization occurs in a native protein and/or affects dephosphorylation of pSer/Thr-Pro motifs. Here we show that the major Pro-directed phosphatase PP2A is conformation-specific and effectively dephosphorylates only thetranspSer/Thr-Pro isomer. Furthermore, Pin1 catalyzes prolyl isomerization of specific pSer/Thr-Pro motifs both in Cdc25C and tau to facilitate their dephosphorylation by PP2A. Moreover, Pin1 and PP2A show reciprocal genetic interactions, and prolyl isomerase activity of Pin1 is essential for cell division in vivo. Thus, phosphorylation-specific prolyl isomerization catalyzed by Pin1 is a novel mechanism essential for regulating dephosphorylation of certain pSer/Thr-Pro motifs.