Singh T J, Grundke-Iqbal I, Iqbal K
New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314.
J Neurochem. 1995 Mar;64(3):1420-3. doi: 10.1046/j.1471-4159.1995.64031420.x.
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.
微管相关蛋白tau在阿尔茨海默病中异常过度磷酸化。脯氨酸依赖性蛋白激酶（PDPKs）和非PDPKs均参与tau的这种过度磷酸化。几种PDPKs可在体外使tau磷酸化，并诱导许多磷酸化依赖性抗体产生阿尔茨海默病样表位。非PDPKs尚未有类似诱导作用的报道。在本研究中，我们评估了六种非PDPKs [环磷酸腺苷依赖性（A激酶）、钙/磷脂依赖性（C激酶）、酪蛋白激酶-1（CK-1）、酪蛋白激酶-2（CK-2）、钙/钙调蛋白依赖性蛋白激酶II以及大鼠小脑钙/钙调蛋白依赖性蛋白激酶]诱导tau产生阿尔茨海默病样表位的能力。A激酶、C激酶、CK-1和CK-2可诱导产生此类表位，但CK-1诱导的程度远大于其他激酶。这些结果表明，CK-1可能在阿尔茨海默病中tau从正常磷酸化状态转变为异常磷酸化状态的过程中起重要作用。
