The microtubule-associated protein tau is also phosphorylated on tyrosine.
Tau protein is the principal component of the neurofibrillary tangles found in Alzheimer's disease (AD), where it is hyperphosphorylated on serine and threonine residues. It is hypothesized that this hyperphosphorylation contributes to neurodegeneration through the destabilization of microtubules. There is now evidence that phosphorylation of tau can also occur on tyrosine residues. Human tau has five tyrosines numbered 18, 29, 197, 310, and 394, according to the sequence of the longest CNS isoform. Tyrosines 18, 197, and 394 have been shown to be phosphorylated in the brain of patients with AD whereas tyrosine 394 is the only residue that has been described to date that is phosphorylated in physiological conditions. Src family kinases and spleen tyrosine kinase (Syk) have been shown to phosphorylate tyrosine 18 while c-Abl is capable of phosphorylating tyrosine 394. Recently, a dual specificity kinase termed TTBK1 has been characterized in human brain and shown to be able to phosphorylate residue 197 of tau. Data about the role of tau tyrosine phosphorylation in neuronal physiology are still scarce and preliminary. In contrast, there is mounting evidence suggesting that tau tyrosine phosphorylation is an early event in the pathophysiology of AD and that Fyn and c-Abl are critical in the neurodegenerative process which occurs in tauopathies.
Lebouvier
Thibaud
T
Inserm, U913, Nantes, France.
Scales
Timothy M E
TM
Williamson
Ritchie
R
Noble
Wendy
W
Duyckaerts
Charles
C
Hanger
Diane P
DP
Reynolds
C Hugh
CH
Anderton
Brian H
BH
Derkinderen
Pascal
P
D000544:Alzheimer Disease / Q000378:metabolism / Q000503:physiopathology; D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008870:Microtubules / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation / Q000235:genetics; D051076:Proto-Oncogene Proteins c-fyn / Q000235:genetics / Q000378:metabolism; D024801:Tauopathies / Q000235:genetics / Q000378:metabolism; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
D016875:tau Proteins; D014443:Tyrosine; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn