Calcium/calmodulin‐dependent protein kinase II phosphorylates tau at Ser‐262 but only partially inhibits its binding to microtubules

FEBS Letters

Singh, Toolsee J.²  Grundke-Iqbal, Inge²  Kontzekova, Eva¹  Wang, Jian-Zhi²  Novak, Michal¹  Iqbal, Khalid² 

[1] Institute of Neuroimmunology, Slovak Academy of Sciences, 842-46 Bratislava, Slovak Republic;New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, NY 10314, USA

关键词: Tau protein;    Microtubule;    Protein kinase;    Alzheimer's disease;    Protein phosphorylation;    PHF;    paired helical filaments;    A-kinase;    cyclic AMP-dependent protein kinase;    CaM kinase II;    calcium/calmodulin-dependent protein kinase II;    C-kinase;    calcium/phospholipid-dependent protein kinase;    CK-1;    casein kinase-1;    GSK-3;    glycogen synthase kinase-3;    MAP kinase;    mitogen-activated protein kinase;    PDPK;    proline-dependent protein kinase;   

DOI  :  10.1016/0014-5793(96)00485-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 (tau₄₁₀). 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.

【 授权许可】

Unknown