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MARKK, a Ste20‐like kinase, activates the polarity‐inducing kinase MARK/PAR‐1
Author(s) -
Timm Thomas,
Li XiaoYu,
Biernat Jacek,
Jiao Jian,
Mandelkow Eckhard,
Vandekerckhove Joel,
Mandelkow EvaMaria
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg447
Subject(s) - biology , microbiology and biotechnology , cyclin dependent kinase 9 , kinase , map kinase kinase kinase , polarity (international relations) , mitogen activated protein kinase kinase , protein kinase a , genetics , cell
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.