RT Journal Article
SR Electronic
T1 Phosphorylation of Tau by Fyn: Implications for Alzheimer's Disease
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 2304
OP 2312
DO 10.1523/JNEUROSCI.4162-03.2004
VO 24
IS 9
A1 Gloria Lee
A1 Ramasamy Thangavel
A1 Vandana M. Sharma
A1 Joel M. Litersky
A1 Kiran Bhaskar
A1 Sandy M. Fang
A1 Lana H. Do
A1 Athena Andreadis
A1 Gary Van Hoesen
A1 Hanna Ksiezak-Reding
YR 2004
UL http://www.jneurosci.org/content/24/9/2304.abstract
AB 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 Aβ 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.