The Alzheimer-like phosphorylation of tau protein reduces microtubule binding and involves Ser-Pro and Thr-Pro motifs

N Gustke; B Steiner; E M Mandelkow; J Biernat; H E Meyer; M Goedert; E Mandelkow

doi:10.1016/0014-5793(92)80767-b

The Alzheimer-like phosphorylation of tau protein reduces microtubule binding and involves Ser-Pro and Thr-Pro motifs

FEBS Lett. 1992 Jul 28;307(2):199-205. doi: 10.1016/0014-5793(92)80767-b.

Authors

N Gustke¹, B Steiner, E M Mandelkow, J Biernat, H E Meyer, M Goedert, E Mandelkow

Affiliation

¹ Max-Planck-Unit for Structural Molecular Biology, c/o DESY, Hamburg, Germany.

PMID: 1644173
DOI: 10.1016/0014-5793(92)80767-b

Abstract

Tau protein can be transformed into an Alzheimer-like state by phosphorylation with a kinase activity from brain [Biernat et al. (1992) EMBO J. 11, 1593-1597]. Here we show that the phosphorylation at Ser-Pro motifs strongly decreases tau's affinity for microtubules. The major reduction occurs during the first of the three main stages of phosphorylation. The data explain the lower stability of microtubules resulting from the pathological tau phosphorylation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease / metabolism*
Amino Acid Sequence
Brain / metabolism
Chromatography, High Pressure Liquid
Electrophoresis, Polyacrylamide Gel
Humans
Microtubules / metabolism*
Molecular Sequence Data
Mutation
Phosphorylation
Proline / metabolism
Protein Binding
Protein Kinases / metabolism
Serine / metabolism
Threonine / metabolism
tau Proteins / chemistry
tau Proteins / metabolism*

Substances

tau Proteins
Threonine
Serine
Proline
Protein Kinases