Affiliations: [a] Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA | [b] Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA | [c] Litwin-Zucker Research Center for the Study of Alzheimer Disease, The Feinstein Institute for Medical Research, North Shore-LIJ, Manhasset, NY, USA
Correspondence:
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Corresponding author: Matthew Tremblay, Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue F526, Bronx, NY 10461, USA. Tel.: +1 718 430 3083; Fax: +1 718 430 8541; E-mail: mtrembla@aecom.yu.edu.
Note: [] Handling Associate Editor: Robert Bowser
Abstract: 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.
