MICROTUBULE-STIMULATED PHOSPHORYLATION OF TAU AT SER202 AND THR205 BYCDK5 DECREASES ITS MICROTUBULE NUCLEATION ACTIVITY

Phosphorylation of tau, a heat-stable neuron-specific microtubule-asso ciated protein, by cdk5 was stimulated in the presence of microtubules (MTs), This stimulation was due to an increased phosphorylation rate and there was no increase in total amount of phosphorylation. Two-dime nsional phosphopeptide map analysis showed that MTs stimulated phospho rylation of a specific peptide. Using Western blotting with antibodies that the recognized phosphorylation-dependent epitopes within tau, th e phosphorylation sites stimulated by the presence of MTs were found t o be Ser202 and Thr205 (numbered according to the human tau isoform co ntaining 441 residues), MT-dependent phosphorylation at Thr205 was obs erved in situ in rat cerebrum primary cultured neurons, Stimulated pho sphorylation at Ser202 and Thr205 decreased the MT-nucleation activity of tau, which is in contrast to MT-independent phosphorylation at Ser 235 and Ser404.