PHOSPHORYLATION OF TAU BY PROLINE-DIRECTED PROTEIN-KINASE (P34(CDC2)/P58(CYCLIN-A)) DECREASES TAU-INDUCED MICROTUBULE ASSEMBLY AND ANTIBODY SMI33 REACTIVITY

被引:42
作者
SCOTT, CW [1 ]
VULLIET, PR [1 ]
CAPUTO, CB [1 ]
机构
[1] UNIV CALIF DAVIS,DEPT VET PHARMACOL & TOXICOL,DAVIS,CA 95616
关键词
ALZHEIMERS DISEASE; CYTOSKELETON; MICROTUBULE-ASSOCIATED PROTEIN;
D O I
10.1016/0006-8993(93)90508-K
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Tau protein was evaluated as a substrate for a proline-directed protein kinase (p34cdc2/p58cyclin A) which recognizes the phosphorylation site motif X-Ser/Thr-Pro-X. The shortest human tau isoform, expressed as a recombinant protein, was phosphorylated to a stoichiometry of 2 mol phosphate/mol tau. Phosphoamino acid analysis revealed phosphorylation of both serine and threonine residues. Phosphorylation of recombinant tau resulted in a decreased ability to induce microtubule assembly but had no effect on the final extent of microtubule formation or on the rate of cold-induced microtubule disassembly. Phosphorylation of tau by the proline-directed protein kinase completely blocked immunoreactivity with antibody SMI33. Phosphorylation did not create the epitopes for the phosphate-dependent antibodies SMI31 or SMI34. Antibody SMI33 recognizes neurofibrillary tangles after treatment with alkaline phosphatase, suggesting that the proline-directed protein kinase may phosphorylate tau at sites that are phosphorylated in Alzheimer's disease.
引用
收藏
页码:237 / 242
页数:6
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