τ Protein Kinase II Is Involved in the Regulation of the Normal Phosphorylation State of τ Protein

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Abstract
To study the phosphorylation state of τ in vivo, we have prepared antisera by immunizing rabbits with synthetic phosphopeptides containing phosphoamino acids at specific sites that are potential targets for τ protein kinase II. Immunoblot experiments using these antisera demonstrated that τ in microtubule‐associated proteins is phosphorylated at Ser144 and at Ser315. Almost all τ variants separated on two‐dimensional gel electrophoresis were phosphorylated at Ser144 and nearly one‐half of them at Ser315. Phosphorylation at Ser144 and at Thr147 of τ isolated from heat‐stable brain extracts was shown to be developmentally regulated, with the highest level of phosphorylation found at postnatal week 1. In vitro phosphorylation of τ by τ protein kinase I, a kinase responsible for abnormal phosphorylation of τ found in paired helical filaments of patients with Alzheimer's disease, was enhanced by prior phosphorylation of τ by τ protein kinase II. Thus, we suggest that τ protein kinase II is indirectly involved, at least in part, in the regulation of the phosphorylation state of τ in neuronal cells.