Lippincott Williams & Wilkins, Inc., Philadelphia
Tau Protein Is Hyperphosphorylated in a Site-Specific Manner in Apoptotic Neuronal PC12 Cells
Article first published online: 29 JUL 2008
Journal of Neurochemistry
Volume 75, Issue 6, pages 2346–2357, December 2000
How to Cite
Zhang, J. and Johnson, G. V. W. (2000), Tau Protein Is Hyperphosphorylated in a Site-Specific Manner in Apoptotic Neuronal PC12 Cells. Journal of Neurochemistry, 75: 2346–2357. doi: 10.1046/j.1471-4159.2000.0752346.x
Abbreviations used: cdc2, cell division control protein kinase;cdk5, cyclin-dependent kinase 5; CK1α, casein kinase 1α; ERK,extracellular regulated kinase; GSK3β, glycogen synthase kinase 3β;HMW, high molecular weight; IEF, isoelectric focusing; MALDI-TOF,matrix-assisted laser desorption ionization-time of flight; NGF, nerve growthfactor; PHF, paired helical filament; RP, reverse-phase; SDS, sodium dodecylsulfate.
- Issue published online: 29 JUL 2008
- Article first published online: 29 JUL 2008
Abstract: Alterations in the status of microtubules contribute tothe cytoskeletal rearrangements that occur during apoptosis. Themicrotubule-associated protein tau regulates microtubule dynamics and thus islikely to play an important role in the cytoskeletal changes that occur inapoptotic cells. Previously, we demonstrated that the phosphorylation of tauat the Tau-1 epitope was increased during neuronal PC12 cell apoptosis, andfurther that the microtubule binding of tau from apoptotic cells wassignificantly impaired because of altered phosphorylation. The fact that themicrotubule-binding capacity of tau from apoptotic cells was reduced to∼30% of control values indicated that sites in addition to those withinthe Tau-1 epitope were hyperphosphorylated during apoptosis. In this studyusing a combination of immunological and biochemical approaches, numeroussites were found to be hyperphosphorylated on tau isolated from apoptoticcells. Further, during apoptosis, the activities of cell division controlprotein kinase (cdc2) and cyclin-dependent kinase 5 (cdk5) were selectivelyand significantly increased. The association of these two protein kinases withtau was also increased during apoptosis. These findings are intriguing becausemany of the sites found to be hyperphosphorylated on tau during apoptosis arealso hyperphosphorylated on tau from Alzheimer's disease brain. Likewise,there are data indicating that in Alzheimer's disease the activities of cdc2and cdk5 are also increased.