title: Phosphorylation of tau protein by casein kinase-1 converts it to an abnormal Alzheimer-like state.
abstract: The microtubule-associated protein tau is abnormally hyperphosphorylated in Alzheimer's disease. Both proline-dependent protein kinases (PDPKs) and non-PDPKs are involved in this hyperphosphorylation of tau. Several PDPKs can phosphorylate tau in vitro and induce Alzheimer-like epitopes to many phosphorylation-dependent antibodies. A similar induction has not been reported with non-PDPKs. In this study we have evaluated six non-PDPKs [cyclic AMP-dependent (A-kinase), calcium/phospholipid-dependent (C-kinase), casein kinase-1 (CK-1), casein kinase-2 (CK-2), calcium/calmodulin-dependent protein kinase II, and calcium/calmodulin-dependent protein kinase from rat cerebellum] for their abilities to induce Alzheimer-like epitopes on tau. Such epitopes were induced by A-kinase, C-kinase, CK-1, and CK-2, but the degree of induction achieved by CK-1 was much greater than with the other kinases. These results suggest that CK-1 may play an important role in the conversion of tau from the normal to the abnormal phosphorylation state in Alzheimer's disease.
authors.affiliation: New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314.
authors.forename: T J
authors.initials: TJ
authors.lastname: Singh
authors.forename: I
authors.initials: I
authors.lastname: Grundke-Iqbal
authors.forename: K
authors.initials: K
authors.lastname: Iqbal
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D047388:Casein Kinases; D002417:Cattle; D000939:Epitopes; D006801:Humans; D066298:In Vitro Techniques; D010750:Phosphoproteins / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D016875:tau Proteins / Q000276:immunology / Q000378:metabolism*
chemical_list: D000939:Epitopes; D010750:Phosphoproteins; D016875:tau Proteins; D011494:Protein Kinases; D047388:Casein Kinases