Phosphorylation of Microtubule-associated Proteins MAP2 and MAP4 by the Protein Kinase p110

doi:10.1074/jbc.271.18.10834

Phosphorylation of Microtubule-associated Proteins MAP2 and MAP4 by the Protein Kinase p110

PHOSPHORYLATION SITES AND REGULATION OF MICROTUBULE DYNAMICS (*)

From the (1)Max-Planck-Unit for Structural Molecular Biology, Notkestrasse 85, D-22603 Hamburg, Germany, the Institut für Physiologische Chemie, Ruhr-Universität, Universitätsstrasse 150, D-44780 Bochum, Germany, and the
(2)Department of Biology, Rochester University, Rochester, New York 14627

^¶ To whom correspondence should be addressed. Tel.: 49-40-89982810; Fax: 49-40-891314; mand{at}mpasmb.desy.de.

Abstract

The phosphorylation of microtubule-associated proteins (MAPs) is thought to be a key factor in the regulation of microtubule stability. We have shown recently that a novel protein kinase, termed p110 microtubule-affinity regulating kinase (“MARK”), phosphorylates microtubule-associated protein tau at the KXGS motifs in the region of internal repeats and causes the detachment of tau from microtubules (Drewes, G., Trinczek, B., Illenberger, S., Biernat, J., Schmitt-Ulms, G., Meyer, H. E., Mandelkow, E.-M., and Mandelkow, E.(1995) J. Biol. Chem. 270, 7679-7688). Here we show that p110 phosphorylates analogous KXGS sites in the microtubule binding domains of the neuronal MAP2 and the ubiquitous MAP4. Phosphorylation in vitro leads to the dissociation of MAP2 and MAP4 from microtubules and to a pronounced increase in dynamic instability. Thus the phosphorylation of the repeated motifs in the microtubule binding domains of MAPs by p110 might provide a mechanism for the regulation of microtubule dynamics in cells.

Footnotes

↵^§ The first two authors contributed equally to this work.
↵* This work was supported by grants from the Deutsche Forschungsgemeinschaft and the Ministry of Science and Technology. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵¹ The abbreviations used are:

MAPs

microtubule-associated proteins

PKA

protein kinase A

PKC

protein kinase C

MAPK

mitogen-activated protein kinase

mark

MAP/microtubule affinity regulating kinase

HV-TLE

high voltage-thin layer electrophoresis

HPLC

high performance liquid chromatography

Pipes

1,4-piperazinediethanesulfonic acid.
↵²G. Drewes, H. E. Meyer, E.-M. Mandelkow, and E. Mandelkow, unpublished data.
↵³R. Godemann, G. Schmitt-Ulms, S. Illenberger, J. Biernat, E.-M. Mandelkow, and E. Mandelkow, unpublished observations.
- Received December 26, 1995.