Phosphorylation of microtubule-associated protein tau by stress-activated protein kinases

Michel Goedert (Lead / Corresponding author), Masato Hasegawa, Ross Jakes, Sean Lawler, Ana Cuenda, Philip Cohen

    Research output: Contribution to journalArticlepeer-review

    265 Citations (Scopus)


    The paired helical filament, which comprises the major fibrous element of the neurofibrillary lesions of Alzheimer's disease, is composed of hyperphosphorylated microtubule-associated protein tau. Many of the hyperphosphorylated sites in tau are serine/threonine-prolines. Here we show that the stress-activated protein (SAP) kinases SAPK1γ (also called JNK1), SAPK2a (also called p38, RK, CSBPs, Mpk2 and Mxi2), SAPK2b (also called p38β), SAPK3 (also called ERK6 and p38γ) and SAPK4 phosphorylate tau at many serine/threonine-prolines, as assessed by the generation of the epitopes of phosphorylation-dependent anti-tau antibodies. Based an initial rates of phosphorylation, tau was found to be a good substrate for SAPK4 and SAPK3, a reasonable substrate for SAPK2b and a relatively poor substrate for SAPK2a and SAPK1γ. Phosphorylation of tau by SAPK3 and SAPK4 resulted in a marked reduction in its ability to promote microtubule assembly. These findings double the number of candidate protein kinases for the hyperphosphorylation of tau in Alzheimer's disease and other neurodegenerative disorders.

    Original languageEnglish
    Pages (from-to)57-62
    Number of pages6
    JournalFEBS Letters
    Issue number1
    Publication statusPublished - 2 Jun 1997


    • Alzheimer's disease
    • Microtubule assembly
    • Stress-activated protein kinase
    • Tau protein

    ASJC Scopus subject areas

    • Biophysics
    • Structural Biology
    • Biochemistry
    • Molecular Biology
    • Genetics
    • Cell Biology


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