PHOSPHORYLATION OF TAU-PROTEIN BY CASEIN KINASE-1 CONVERTS IT TO AN ABNORMAL ALZHEIMER-LIKE STATE

The microtubule-associated protein tau is abnormally hyperphosphorylat ed in Alzheimer's disease. Both proline-dependent protein kinases (PDP Ks) and non-PDPKs are involved in this hyperphosphorylation of tau. Se veral PDPKs can phosphorylate tau in vitro and induce Alzheimer-like e pitopes to many phosphorylation-dependent antibodies. A similar induct ion has not been reported with non-PDPKs. In this study we have evalua ted six non-PDPKs [cyclic AMP-dependent (A-kinase), calcium/phospholip id-dependent (C-kinase), casein kinase-1 (CK-1), casein kinase-2 (CK-2 ), calcium/calmodulin-dependent protein kinase II, and calcium/calmodu lin-dependent protein kinase from rat cerebellum] for their abilities to induce Alzheimer-like epitopes on tau. Such epitopes were induced b y A-kinase, C-kinase, CK-I, and CK-2, but the degree of induction achi eved by CK-I was much greater than with the other kinases. These resul ts suggest that CK-I may play an important role in the conversion of t au from the normal to the abnormal phosphorylation state in Alzheimer' s disease.