MARKK, a Ste20-like kinase, activates the polarity-inducing kinase MARK/PAR-1
MARKK, a Ste20-like kinase, activates the polarity-inducing kinase MARK/PAR-1
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DOI：
10.1093/emboj/cdg447
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发表时间：
2003-10-01
期刊：
影响因子：
11.4
通讯作者：
Mandelkow, EM
中科院分区：
文献类型：
--
作者：
Timm, T;Li, XY;Mandelkow, EM
MARK是一个与PAR-1相关的激酶家族，参与建立细胞极性，磷酸化KXGS基序上的微管相关蛋白（tau/MAP2/MAP4），导致微管脱离和解体。这些位点在阿尔茨海默病大脑中的tau蛋白中很突出。我们研究了MARK的活化，并确定了上游激酶MARKK，它是Ste20激酶家族的成员。它在活化环中磷酸化MARK （MARK2中的T208）。脑组织中MARK的一部分被双重磷酸化（在T208/S212），让人想起MAP激酶的激活；然而，MARK中第二个位点（S212）的磷酸化是抑制性的。在细胞中，MARKK的活性通过激活MARK增强微管动力学，并导致磷酸化和微管上tau或等效map的分离。MARK的过度表达最终导致微管破裂和细胞死亡，但在神经元细胞中，其主要作用是在分化过程中允许神经突的发育。
MARK, a kinase family related to PAR-1 involved in establishing cell polarity, phosphorylates microtubule-associated proteins (tau/MAP2/MAP4) at KXGS motifs, causes detachment from microtubules, and their disassembly. The sites are prominent in tau from Alzheimer's disease brains. We studied the activation of MARK and identified the upstream kinase, MARKK, a member of the Ste20 kinase family. It phosphorylates MARK within the activation loop (T208 in MARK2). A fraction of MARK in brain tissue is doubly phosphorylated (at T208/S212), reminiscent of the activation of MAP kinase; however, the phosphorylation of the second site in MARK (S212) is inhibitory. In cells the activity of MARKK enhances microtubule dynamics through the activation of MARK and leads to phosphorylation and detachment of tau or equivalent MAPs from microtubules. Overexpression of MARK eventually leads to microtubule breakdown and cell death, but in neuronal cells the primary effect is to allow the development of neurites during differentiation.