|The retinoic acid and brain-derived neurotrophic factor differentiated SH-SY5Y cell line as a model for Alzheimer's disease-like tau phosphorylation. |
Jämsä, A., et al.
Biochem. Biophys. Res. Comm., 319:993-1000 (2004)
|Involvement of aberrant glycosylation in phosphorylation of tau by cdk5 and GSK-3beta. |
Liu, F., et al.
FEBS Lett., 530(1-3):209-214 (2002)
|Interaction of tau isoforms with Alzheimer's disease abnormally hyperphosphorylated tau and in vitro phosphorylation into the disease-like protein. |
Alonso, A.D., et al.
J. Biol. Chem., 276(41):37967-37973 (2001)
|Distribution of tau protein kinase I/glycogen synthase kinase-3beta, phosphatases 2A and 2B, and phosphorylated tau in the developing rat brain. |
Takahashi, M., et al.
Brain Res., 857(1-2):193-206 (2000)
|Tau is phosphorylated by GSK-3 at several sites found in Alzheimer disease and its biological activity markedly inhibited only after it is prephosphorylated by A-kinase. |
Wang, J.Z., et al.
FEBS Lett., 436(1):28-34 (1998)
|Reactivating kinase/p38 phosphorylates tau protein in vitro. |
Reynolds, C.H., et al.
J. Neurochem., 69(1):191-198 (1997)
|Stress-activated protein kinase/c-jun N-terminal kinase phosphorylates tau protein. |
Reynolds, C H, et al.
J. Neurochem., 68: 1736-44 (1997)
A proportion of the neuronal microtubule-associated protein (MAP) tau is highly phosphorylated in foetal and adult brain, whereas the majority of tau in the neurofibrillary tangles of Alzheimer's patients is hyperphosphorylated; many of the phosphorylation sites are serines or threonines followed by prolines. Several kinases phosphorylate tau at such sites in vitro. We have now shown that purified recombinant stress-activated protein kinase/c-Jun N-terminal kinase, a proline-directed kinase of the MAP kinase extended family, phosphorylates recombinant tau in vitro on threonine and serine residues. Western blots using antibodies to phosphorylation-dependent tau epitopes demonstrated that phosphorylation occurs in both of the main phosphorylated regions of tau protein. Unlike glycogen synthase kinase-3, the c-Jun N-terminal kinase readily phosphorylates Thr205 and Ser422, which are more highly phosphorylated in Alzheimer tau than in foetal or adult tau. Glycogen synthase kinase-3 may preferentially phosphorylate the sites found physiologically, in foetal and to a smaller extent in adult tau, whereas stress-activated/c-Jun N-terminal kinase and/or other members of the extended MAP kinase family may be responsible for pathological proline-directed phosphorylations. Inflammatory processes in Alzheimer brain might therefore contribute directly to the pathological formation of the hyperphosphorylated tau found in neurofibrillary tangles.
|Physiology and pathology of tau protein kinases in relation to Alzheimer's disease. |
Imahori, K. and T. Uchida
J. Biochem., 121:179-188 (1997)
|Regulation of the phosphorylation state and microtubule-binding activity of tau by protein phosphatase 2A. |
Sontag, E., et al.
Neuron , 17:1201-1207 (1996)