PMID:7706316

Citation	Drewes, G, Trinczek, B, Illenberger, S, Biernat, J, Schmitt-Ulms, G, Meyer, HE, Mandelkow, EM and Mandelkow, E (1995) Microtubule-associated protein/microtubule affinity-regulating kinase (p110mark). A novel protein kinase that regulates tau-microtubule interactions and dynamic instability by phosphorylation at the Alzheimer-specific site serine 262. J. Biol. Chem. 270:7679-88
Abstract	Aberrant phosphorylation of the microtubule-associated protein tau is one of the pathological features of neuronal degeneration in Alzheimer's disease. The phosphorylation of Ser-262 within the microtubule binding region of tau is of particular interest because so far it is observed only in Alzheimer's disease (Hasegawa, M., Morishima-Kawashima, M., Takio, K., Suzuki, M., Titani, K., and Ihara, Y. (1992) J. Biol. Chem. 26, 17047-17054) and because phosphorylation of this site alone dramatically reduces the affinity for microtubules in vitro (Biernat, J., Gustke, N., Drewes, G., Mandelkow, E.-M., and Mandelkow, E. (1993) Neuron 11, 153-163). Here we describe the purification and characterization of a protein-serine kinase from brain tissue with an apparent molecular mass of 110 kDa on SDS gels. This kinase specifically phosphorylates tau on its KIGS or KCGS motifs in the repeat domain, whereas no significant phosphorylation outside this region was detected. Phosphorylation occurs mainly on Ser-262 located in the first repeat. This largely abolishes tau's binding to microtubules and makes them dynamically unstable, in contrast to other protein kinases that phosphorylate tau at or near the repeat domain. The data suggest a role for this novel kinase in cellular events involving rearrangement of the microtuble-associated proteins/microtubule arrays and their pathological degeneration in Alzheimer's disease.
Links	PubMed
Keywords	Alzheimer Disease/metabolism; Amino Acid Sequence; Animals; Brain/enzymology; Chromatography, Ion Exchange; Cloning, Molecular; Escherichia coli; Humans; Kinetics; Microtubules/metabolism; Molecular Sequence Data; Peptide Fragments/chemistry; Peptide Fragments/isolation & purification; Peptide Mapping; Phosphopeptides/chemistry; Phosphopeptides/isolation & purification; Phosphorylation; Phosphoserine/analysis; Protein-Serine-Threonine Kinases/isolation & purification; Protein-Serine-Threonine Kinases/metabolism; Recombinant Proteins/biosynthesis; Recombinant Proteins/isolation & purification; Recombinant Proteins/metabolism; Serine; Swine; Trypsin; Tubulin/isolation & purification; Tubulin/metabolism; tau Proteins/biosynthesis; tau Proteins/isolation & purification; tau Proteins/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:TAU	involved_in	GO:0031116: positive regulation of microtubule polymerization	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:TAU		GO:0031116: positive regulation of microtubule polymerization	ECO:0000314:		P		Figure 8	complete CACAO 9384

References

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