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Calcium/calmodulin‐dependent protein kinase II phosphorylates tau at Ser‐262 but only partially inhibits its binding to microtubules
Author(s) -
Singh Toolsee J.,
Wang Jian-Zhi,
Novak Michal,
Kontzekova Eva,
Grundke-Iqbal Inge,
Iqbal Khalid
Publication year - 1996
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(96)00485-1
Subject(s) - phosphorylation , kinase , calmodulin , microtubule , cyclin dependent kinase 2 , protein kinase a , chemistry , map2k7 , mitogen activated protein kinase kinase , map kinase kinase kinase , microbiology and biotechnology , biology , biochemistry , enzyme
PHF‐tau, which is phosphorylated at 10 Ser/Thr‐Pro and 11 non‐Ser/Thr‐Pro sites, is unable to promote microtubule assembly. Phosphorylation of the non‐Ser/Thr‐Pro site, Ser‐262, is reported to be primarily responsible for this. The identities of kinase(s) responsible for Ser‐262 phosphorylation are still to be clarified. In this study we have used the monoclonal antibody 12E8, which recognizes P‐Ser‐262 and P‐Ser‐356 on tau, to survey different kinases for their abilities to phosphorylate Ser‐262 on human tau 3L (tau 410 ). In decreasing order of effectiveness we found that Ser‐262 and Ser‐356 phosphorylation can be catalyzed by CaM kinase II ⪢ C‐kinase ⪢ GSK‐3 ≌ A‐kinase ⪢ CK‐1. CaM kinase II and C‐kinase were shown to phosphorylate both Ser‐262 and Ser‐356. The binding of tau to taxol‐stabilized microtubules was decreased by 35 and 42% after phosphorylation by CaM kinase II and C‐kinase, respectively. Of the fraction of tau that bound to microtubules, about 50% was phosphorylated at Ser‐262 and Ser‐356. These results suggest that Ser‐262 and Ser‐356 are very good substrates for CaM kinase II but their phosphorylations are not sufficient to achieve maximal inhibition of tau binding to microtubules.