Tau protein kinase II is involved in the regulation of the normal phosphorylation state of tau protein.
To study the phosphorylation state of tau in vivo, we have prepared antisera by immunizing rabbits with synthetic phosphopeptides containing phosphoamino acids at specific sites that are potential targets for tau protein kinase II. Immunoblot experiments using these antisera demonstrated that tau in microtubule-associated proteins is phosphorylated at Ser144 and at Ser315. Almost all tau 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 tau 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 tau by tau protein kinase I, a kinase responsible for abnormal phosphorylation of tau found in paired helical filaments of patients with Alzheimer's disease, was enhanced by prior phosphorylation of tau by tau protein kinase II. Thus, we suggest that tau protein kinase II is indirectly involved, at least in part, in the regulation of the phosphorylation state of tau in neuronal cells.
Arioka
M
M
Mitsubishi Kasei Institute of Life Sciences, Tokyo, Japan.
Tsukamoto
M
M
Ishiguro
K
K
Kato
R
R
Sato
K
K
Imahori
K
K
Uchida
T
T
D000375:Aging / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D002417:Cattle; D051360:Cyclin-Dependent Kinase 5; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D007106:Immune Sera; D015151:Immunoblotting; D008969:Molecular Sequence Data; D010748:Phosphopeptides / Q000138:chemical synthesis / Q000276:immunology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012694:Serine; D013379:Substrate Specificity; D013912:Threonine; D016875:tau Proteins / Q000378:metabolism*
D007106:Immune Sera; D010748:Phosphopeptides; D016875:tau Proteins; D013912:Threonine; D012694:Serine; D051360:Cyclin-Dependent Kinase 5; D017346:Protein Serine-Threonine Kinases; C079134:tau protein kinase II