Tau protein is hyperphosphorylated in a site-specific manner in apoptotic neuronal PC12 cells.
Alterations in the status of microtubules contribute to the cytoskeletal rearrangements that occur during apoptosis. The microtubule-associated protein tau regulates microtubule dynamics and thus is likely to play an important role in the cytoskeletal changes that occur in apoptotic cells. Previously, we demonstrated that the phosphorylation of tau at the Tau-1 epitope was increased during neuronal PC12 cell apoptosis, and further that the microtubule binding of tau from apoptotic cells was significantly impaired because of altered phosphorylation. The fact that the microtubule-binding capacity of tau from apoptotic cells was reduced to approximately 30% of control values indicated that sites in addition to those within the Tau-1 epitope were hyperphosphorylated during apoptosis. In this study using a combination of immunological and biochemical approaches, numerous sites were found to be hyperphosphorylated on tau isolated from apoptotic cells. Further, during apoptosis, the activities of cell division control protein kinase (cdc2) and cyclin-dependent kinase 5 (cdk5) were selectively and significantly increased. The association of these two protein kinases with tau was also increased during apoptosis. These findings are intriguing because many of the sites found to be hyperphosphorylated on tau during apoptosis are also hyperphosphorylated on tau from Alzheimer's disease brain. Likewise, there are data indicating that in Alzheimer's disease the activities of cdc2 and cdk5 are also increased.
Zhang
J
J
Department of Psychiatry and Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0017, USA.
Johnson
G V
GV
D000818:Animals; D017209:Apoptosis; D001665:Binding Sites; D016203:CDC2 Protein Kinase / Q000378:metabolism; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D016716:PC12 Cells; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021122:Protein Subunits; D051381:Rats; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism*
D021122:Protein Subunits; D016875:tau Proteins; D051360:Cyclin-Dependent Kinase 5; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; C495907:Cdk5 protein, rat; D018844:Cyclin-Dependent Kinases