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【Nature oncogene编译】Polo-like激酶的结构和功能
Review
标题：Polo-like激酶的结构和功能
Structure and function of Polo-like kinases
Abstract
Polo-like kinases play critical roles during multiple stages of cell cycle progression. All Polo-like kinases contain an N-terminal Ser/Thr kinase catalytic domain and a C-terminal region that contains one or two Polo-boxes. For Polo-like kinase 1, 2, and 3, and their homologs, the entire C-terminal region, including both Polo-boxes, functions as a single modular phosphoserine/threonine-binding domain known as the Polo-box domain (PBD). In the absence of a bound substrate, the PBD inhibits the basal activity of the kinase domain. Phosphorylation-dependent binding of the PBD to its ligands releases the kinase domain, while simultaneously localizing Polo-like kinases to specific subcellular structures. These observations suggest two different models for how the PBD integrates signals arising from other mitotic kinases to target the activated kinase towards distinct substrates. The recent X-ray crystal structures of the PBD provide insights into the structural basis for PBD function and kinase regulation. Molecular modelling of the structure of the isolated kinase domain reveals a potential basis for motif-dependent substrate specificity.
Keywords
Polo-like kinase; polo-box domain; mitosis; phosphorylation-dependent binding; modular signalling domain
编译：
Polo-like激酶在细胞周期的不同阶段中发挥着重要的作用。所有的Polo-like激酶都包含一个N末端丝氨酸/苏氨酸(Ser/Thr)蛋白激酶催化活性结构域和一个C末端结构域，其中包含了1－2个Polo-boxes。对于Polo-like激酶1，2，3以及它们的同系物来说，整个C末端结构域，包含两个Polo-boxes，其功能是作为一个单模式的磷酸化丝苏氨酸结合的结构域，被称之为PBD。在缺乏一个结合底物的情况下，PBD抑制了激酶结构域的基本活性。而PBD磷酸化作用依赖的配体结合方式可以使得激酶结构域开放，同时使得Polo-like 激酶在特异性的亚细胞结构当中局限化。这些观察结构表明，存在两种不同的模型，是关于PBD是如何结合来自于其他有丝分裂激酶的信号的，并进而通过不同的底物激活它们。最新的有关PBD的X衍射晶体结构则为PBD功能和激酶调控的结构基础提供了新的见解。所分离的激酶结构域结构的分子模型揭示了以模序依赖的底物特异性的潜在的基础。 Polo-like激酶的结构和功能
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作者:admin@医学,生命科学 2011-06-21 05:14
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