Phosphorylation of tau by fyn: implications for Alzheimer's disease

Gloria Lee; Ramasamy Thangavel; Vandana M Sharma; Joel M Litersky; Kiran Bhaskar; Sandy M Fang; Lana H Do; Athena Andreadis; Gary Van Hoesen; Hanna Ksiezak-Reding

doi:10.1523/JNEUROSCI.4162-03.2004

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Phosphorylation of tau by fyn: implications for Alzheimer's disease

Journal article

Open access

Peer reviewed

Phosphorylation of tau by fyn: implications for Alzheimer's disease

Gloria Lee, Ramasamy Thangavel, Vandana M Sharma, Joel M Litersky, Kiran Bhaskar, Sandy M Fang, Lana H Do, Athena Andreadis, Gary Van Hoesen and Hanna Ksiezak-Reding

The Journal of neuroscience, Vol.24(9), pp.2304-2312

03/03/2004

DOI: 10.1523/JNEUROSCI.4162-03.2004

PMCID: PMC6730442

PMID: 14999081

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Abstract

The abnormal phosphorylation of tau protein on serines and threonines is a hallmark characteristic of the neurofibrillary tangles of Alzheimer's disease (AD). The discovery that tau could be phosphorylated on tyrosine and evidence that Abeta signal transduction involved tyrosine phosphorylation led us to question whether tyrosine phosphorylation of tau occurred during the neurodegenerative process. In this study we determined that human tau tyr18 was phosphorylated by the src family tyrosine kinase fyn. By developing both polyclonal and monoclonal probes specific for phospho-tyr18, we found that the phosphorylation of tau at tyr18 occurred at early developmental stages in mouse but was absent in the adult. Our phosphospecific probes also revealed that paired helical filament preparations exhibited phospho-tyr18 reactivity that was sensitive to phosphotyrosine-specific protein phosphatase treatment. Moreover, immunocytochemical studies indicated that tyrosine phosphorylated tau was present in the neurofibrillary tangles in AD brain. However, the staining pattern excluded neuropil threads and dystrophic neurites indicating that tyrosine phosphorylated tau was distributed in AD brain in a manner dissimilar from other abnormally phosphorylated tau. We also found evidence suggesting that differentially phosphorylated tau existed within degenerating neurons. Our data add new support for a role for fyn in the neurodegenerative process.

Immunohistochemistry

Proto-Oncogene Proteins - metabolism

Antibody Specificity

Cell Line

Phosphorylation

Age Factors

tau Proteins - immunology

Humans

Proto-Oncogene Proteins c-fyn

Cercopithecus aethiops

tau Proteins - metabolism

Antibody Affinity

Protein Tyrosine Phosphatases - metabolism

Nerve Degeneration - metabolism

Nerve Degeneration - pathology

Alzheimer Disease - pathology

Brain - metabolism

Microtubules - metabolism

Tyrosine - metabolism

Animals

Alzheimer Disease - metabolism

Brain - pathology

Mice

Antibodies, Monoclonal - metabolism

Details

Title: Subtitle: Phosphorylation of tau by fyn: implications for Alzheimer's disease
Creators: Gloria Lee - Department of Internal Medicine, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa 52242, USA. gloria-lee@uiowa.edu
Ramasamy Thangavel
Vandana M Sharma
Joel M Litersky
Kiran Bhaskar
Sandy M Fang
Lana H Do
Athena Andreadis
Gary Van Hoesen
Hanna Ksiezak-Reding
Resource Type: Journal article
Publication Details: The Journal of neuroscience, Vol.24(9), pp.2304-2312
Publisher: United States
DOI: 10.1523/JNEUROSCI.4162-03.2004
PMID: 14999081
PMCID: PMC6730442
ISSN: 0270-6474
eISSN: 1529-2401
Grant note: AG17753 / NIA NIH HHS
Language: English
Date published: 03/03/2004
Academic Unit: Neurology; Iowa Neuroscience Institute; Immunology; Internal Medicine
Record Identifier: 9984065391902771

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