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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Phosphorylation Keeps Pten Phosphatase Closed For Business
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Phosphorylation Keeps Pten Phosphatase Closed For Business

机译:磷酸化使Pten磷酸酶保持关闭状态

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摘要

Phosphatase and tensin homo-logue deleted on chromosome 10 (PTEN) is a phosphatase that suppresses many tumor types (1, 2). It plays a major role in the development of the nervous system and has been implicated in diseases such as autism (3). Despite its importance, we are only beginning to understand how this important protein is regulated. In 2000 and 2001, Vazquez et al. (4, 5) with great insight proposed that phosphorylation of the C terminus induces PTEN to assume a closed conformation with an inactive phosphatase domain. Upon dephosphorylation, PTEN assumes an open conformation, activating the phosphatase domain and enhancing degradation of PTEN protein. In this view, the phosphorylated closed form acts like a proenzyme, which is stable in the cytoplasm but ready for rapid activation, use, and degradation. Although not fully proven, this model (Fig. 1) has greatly influenced the PTEN field. The study in a recent issue of PNAS by Rah-dar et al. (6) provides convincing proof for this model and new exciting insights into the interactions of PTEN with biological membranes.
机译:在10号染色体(PTEN)上缺失的磷酸酶和张力蛋白同源物是一种抑制许多肿瘤类型的磷酸酶(1、2)。它在神经系统的发育中起着重要作用,并与自闭症等疾病有关(3)。尽管它很重要,我们才刚刚开始了解这种重要蛋白质是如何调节的。在2000年和2001年,Vazquez等人。 (4,5)有深刻的见解提出,C末端的磷酸化可诱导PTEN呈现与无活性磷酸酶结构域的封闭构象。在去磷酸化后,PTEN呈现开放构象,从而激活磷酸酶结构域并增强PTEN蛋白的降解。按照这种观点,磷酸化的封闭形式就像酶一样,在细胞质中是稳定的,但可以快速激活,使用和降解。尽管尚未得到充分证明,但该模型(图1)极大地影响了PTEN领域。 Rah-dar等人在最近一期的PNAS中进行了这项研究。 (6)为该模型提供了令人信服的证据,并为PTEN与生物膜之间的相互作用提供了令人兴奋的新见解。

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