title: Phosphorylation of microtubule-associated proteins MAP2 and MAP4 by the protein kinase p110mark. Phosphorylation sites and regulation of microtubule dynamics.
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 p110mark 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 p110mark might provide a mechanism for the regulation of microtubule dynamics in cells.
authors.affiliation: Max-Planck-Unit for Structural Molecular Biology, Hamburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Illenberger
authors.forename: G
authors.initials: G
authors.lastname: Drewes
authors.forename: B
authors.initials: B
authors.lastname: Trinczek
authors.forename: J
authors.initials: J
authors.lastname: Biernat
authors.forename: H E
authors.initials: HE
authors.lastname: Meyer
authors.forename: J B
authors.initials: JB
authors.lastname: Olmsted
authors.forename: E M
authors.initials: EM
authors.lastname: Mandelkow
authors.forename: E
authors.initials: E
authors.lastname: Mandelkow
mesh_terms: D000818:Animals; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000502:physiology*; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats
chemical_list: D008869:Microtubule-Associated Proteins; C484552:Mark1 protein, rat; D017346:Protein Serine-Threonine Kinases