The prostate-derived sterile 20-like kinase (PSK) regulates microtubule organization and stability
The prostate-derived sterile 20-like kinase (PSK) regulates microtubule organization and stability
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DOI：
10.1074/jbc.m213064200
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发表时间：
2003-05-16
影响因子：
4.8
通讯作者：
Morris, JDH
中科院分区：
文献类型：
--
作者：
Mitsopoulos, C;Zihni, C;Morris, JDH
已知无菌20（STE 20）蛋白激酶，包括生发中心激酶和p21活化蛋白激酶，激活促分裂原活化蛋白激酶途径（c-Jun NH 2-末端激酶，p38，或细胞外信号调节激酶），导致基因转录的变化。一些STE 20也可以调节细胞骨架，我们已经表明，生发中心激酶样激酶前列腺衍生的STE 20样激酶（PSK）影响肌动蛋白细胞骨架组织。在这里，我们证明PSK与微管共定位，这种定位被破坏的微管解聚剂诺考达唑。PSK与微管的缔合导致产生稳定的核周微管缆，其是诺考达唑抗性的并且含有增加水平的乙酰化α-微管蛋白。激酶缺陷型PSK（K57 A）或PSK的C末端（氨基酸745-1235）缺乏激酶结构域足以用于微管结合和稳定，表明不需要蛋白质的催化活性。PSK通过其C末端定位于微管，并且PSK在体外结合并磷酸化α-和β-微管蛋白。PSK（1-940）的N末端不能结合或稳定微管，表明PSK必须与微管结合才能进行重组。这些结果表明，PSK与微管相互作用，影响其组织和稳定性的PSK激酶活性独立。
Sterile 20 (STE20) protein kinases, which include germinal center kinases and p21-activated protein kinases, are known to activate mitogen-activated protein kinase pathways (c-Jun NH2-terminal kinase, p38, or extracellular signal-regulated kinase), leading to changes in gene transcription. Some STE20s can also regulate the cytoskeleton, and we have shown that the germinal center kinase-like kinase prostate-derived STE20-like kinase (PSK) affects actin cytoskeletal organization. Here, we demonstrate that PSK colocalizes with microtubules; and that this localization is disrupted by the microtubule depolymerizing agent nocodazole. The association of PSK with microtubules results in the production of stabilized perinuclear microtubule cables that are nocodazole-resistant and contain increased levels of acetylated alpha-tubulin. Kinase-defective PSK (K57A) or the C terminus of PSK (amino acids 745-1235) lacking the kinase domain are sufficient for microtubule binding and stabilization, demonstrating that the catalytic activity of the protein is not required. The localization of PSK to microtubules occurs via its C terminus, and PSK binds and phosphorylates alpha- and beta-tubulin in vitro. The N terminus of PSK (1-940) is unable to bind or stabilize microtubules, demonstrating that PSK must associate with microtubules for their reorganization to occur. These results demonstrate that PSK interacts with microtubules and affects their organization and stability independently of PSK kinase activity.