Differential effects of apolipoprotein E isoforms on phosphorylation at specific sites on tau by glycogen synthase kinase-3 beta identified by nano-electrospray mass spectrometry

Previously published data have shown an allele-specific variation in the in vitro binding of apolipoprotein E (apoE) to tau, which prompted the hypoth esis that apoE binding may protect tau from phosphorylation, apoE3 being mo re efficient than apoE4, We have, therefore, investigated the effects of ap oE on tau phosphorylation in vitro by the proline-directed kinase, glycogen synthase kinase (GSK)-3 beta The phosphopeptide maps of tau alone, of tau with apoE3 and of tau with apoE4 were very similar. When apoE2 was present a further four spots were evident. Additionally, of the 15 peptides phospho rylated in the presence or absence of apoE, subtle differences, some isofor m-specific, in the relative amounts of phosphorylation were observed. (C) 2 000 Federation of European Biochemical Societies, Published by Elsevier Sci ence B.V. All rights reserved.