Tau phosphorylated at tyrosine 394 is found in Alzheimer's disease tangles and can be a product of the Abl-related kinase, Arg.
Tau is a microtubule-associated protein and a main component of neurofibrillary tangles, one of the pathologic hallmarks of Alzheimer's disease. The paired helical filaments (PHF) that comprise neurofibrillary tangles contain an abnormally hyperphosphorylated form of tau. Historically, most of the tau phosphorylation sites that have been characterized are serine and threonine residues. Recent reports state that tau can be phosphorylated at tyrosine residues by kinases including Fyn, Syk, and c-abl (Abl). Proteomic analyses show that tau phosphorylated at tyrosine 394 (Y394) exists within PHF samples taken from Alzheimer's disease brains. This study also confirms phosphorylation of Y394 as an Alzheimer's disease-specific event by immunohistochemistry. To date, only Abl is known to phosphorylate this particular site on tau. We report, for the first time, that Arg, the other member of the Abl family of tyrosine kinases, also phosphorylates tau at Y394 in a manner independent of Abl activity. Given the reported role of Arg in oxidative stress response and neural development, the ability to phosphorylate tau at Y394 implicates Arg as a potential player in the pathogenesis of Alzheimer's disease and other tauopathies.
Tremblay
Matthew A
MA
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. mtrembla@aecom.yu.edu
Acker
Christopher M
CM
Davies
Peter
P
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000544:Alzheimer Disease / Q000473:pathology*; D000704:Analysis of Variance; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D008870:Microtubules / Q000378:metabolism; D009447:Neuroblastoma / Q000473:pathology; D016874:Neurofibrillary Tangles / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism; D013997:Time Factors; D014162:Transfection / Q000379:methods; D014443:Tyrosine / Q000378:metabolism*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
D016875:tau Proteins; D014443:Tyrosine; D000255:Adenosine Triphosphate; C426236:ARG tyrosine kinase; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl