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Tau Protein Is Hyperphosphorylated in a Site‐Specific Manner in Apoptotic Neuronal PC12 Cells
Author(s) -
Zhang Jianwen,
Johnson Gail V. W.
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0752346.x
Subject(s) - tau protein , cyclin dependent kinase 5 , microbiology and biotechnology , apoptosis , kinase , biology , microtubule , phosphorylation , cyclin dependent kinase 1 , cytoskeleton , microtubule associated protein , cell cycle , protein kinase a , alzheimer's disease , cell , cyclin dependent kinase 2 , biochemistry , medicine , disease
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.