In Alzheimer disease brain the microtubule associated protein (MAP) τ is abnormally hyperphosphorylated. The role of protein phosphatases (PP) in the regulation of phosphorylation of τ was studied in undifferentiated SY5Y cells. In cells treated with 10 nM okadaic acid (OA), a PP-2A/PP-1 inhibitor, the PP- 1 and -2A activities decreased by 60% and 100% respectively and the activities of MAPKs, cdc2 kinase and cdk5, but not of GSK- 3, increased. OA increased the phosphorylation of τ at Thr-231/Ser-235 and Ser-396/404, but not at Ser-262/356 or Ser-199/202. An increase in tyrosinated-detyrosinated tubulin ratio, a decrease (in the microtubule binding activities of x, MAP1b and MAP2, and cell death were observed. Treatment with 1 gm taxol c partially inhibited the cell death. These data suggest (1) that OA induced hyperphosphorylation of x is probably the result of r activated MAPK and cdks in addition to decreased PP-2A and PP-I activities and (2) that in SY5Y cells the OA induced cell death is associated with a decrease in stable microtubules.
Tanaka, T., Zhong, J., Iqbal, K., Trenkner, E., & Grundke-Iqbal, I. (1998). The regulation of phosphorylation of τ in SY5Y neuroblastoma cells: The role of protein phosphatases. FEBS Letters, 426(2), 248–254. https://doi.org/10.1016/S0014-5793(98)00346-9