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A more recent version of this article appeared on November 1, 2002
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Submitted on March 26, 2002
Revised on July 25, 2002
Accepted on August 21, 2002
1 Max-Planck-Unit for Structural Molecular Biology, c/o DESY, Notkestrasse 85, D-22607 Hamburg, Germany
2 CNRS, Station Biologique, BP 74, F-29682 Roscoff cedex, France
* Corresponding author. E-mail address: mand{at}mpasmb.desy.de.
Protein kinases of the MARK family were originally discovered because of their ability to phosphorylate certain sites in tau protein (KXGS motifs in the repeat domain). This type of phosphorylation is enhanced in abnormal tau from Alzheimer brain tissue and causes the detachment of tau from microtubules. MARK-related kinases (PAR-1, KIN1) occur in various organisms and are involved in establishing and maintaining cell polarity. Here we report the ability of MARK2 to affect the differentiation and outgrowth of cell processes from neuroblastoma and other cell models. MARK2 phosphorylates tau protein at the KXGS motifs; this results in the detachment of tau from microtubules and their destabilization. The formation of neurites in N2a cells is blocked if MARK2 is inactivated, either by transfecting a dominant negative mutant, or by MARK2 inhibitors such as hymenialdisine. Alternatively, neurites are blocked if the target KXGS motifs on tau are rendered non-phosphorylatable by point mutations. The results suggest that MARK2 contributes to the plasticity of microtubules needed for neuronal polarity and the growth of neurites.
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