Tyrosine Phosphorylation of Tau by the SRC Family Kinases Lck and Fyn

Overview

Journal Mol Neurodegener

Publisher Biomed Central

Specialties Molecular Biology
Neurology

Date 2011 Jan 29

PMID 21269457

Citations 26

Authors

Timothy Me Scales

Pascal Derkinderen

Kit-Yi Leung

Helen L Byers

Malcolm A Ward

Caroline Price

Ian N Bird

Timothy Perera

Stuart Kellie

Ritchie Williamson

Brian H Anderton

C Hugh Reynolds

Affiliations

Soon will be listed here.

Abstract

Background: Tau protein is the principal component of the neurofibrillary tangles found in Alzheimer's disease, where it is hyperphosphorylated on serine and threonine residues, and recently phosphotyrosine has been demonstrated. The Src-family kinase Fyn has been linked circumstantially to the pathology of Alzheimer's disease, and shown to phosphorylate Tyr18. Recently another Src-family kinase, Lck, has been identified as a genetic risk factor for this disease.

Results: In this study we show that Lck is a tau kinase. In vitro, comparison of Lck and Fyn showed that while both kinases phosphorylated Tyr18 preferentially, Lck phosphorylated other tyrosines somewhat better than Fyn. In co-transfected COS-7 cells, mutating any one of the five tyrosines in tau to phenylalanine reduced the apparent level of tau tyrosine phosphorylation to 25-40% of that given by wild-type tau. Consistent with this, tau mutants with only one remaining tyrosine gave poor phosphorylation; however, Tyr18 was phosphorylated better than the others.

Conclusions: Fyn and Lck have subtle differences in their properties as tau kinases, and the phosphorylation of tau is one mechanism by which the genetic risk associated with Lck might be expressed pathogenically.

Citing Articles

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Tyrosine kinases: multifaceted receptors at the intersection of several neurodegenerative disease-associated processes.

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