Implication of brain cdc2 and MAP2 kinases in the phosphorylation of tau protein in Alzheimer's disease.
Brain tau protein is phosphorylated in vitro by cdc2 and MAP2 kinases, obtained through immunoaffinity purification from rat brain extracts. The phosphorylation sites are located on the tau molecule both upstream and downstream of the tubulin-binding motifs. A synthetic peptide comprising residues 194-213 of the tau sequence, which contains the epitope recognized by the monoclonal antibody tau-1, is also efficiently phosphorylated in vitro by cdc2 and MAP2 kinases. Phosphorylation of this peptide markedly reduces its interaction with the antibody tau-1, as it has been described for tau protein in Alzheimer's disease. Both cdc2 and MAP2 kinases are present in brain extracts obtained from Alzheimer's disease patients. Interestingly, the level of cdc2 kinase may be increased in patient brains as compared with non-demented controls. These results suggest a role for cdc2 and MAP2 kinases in phosphorylating tau protein at the tau-1 epitope in Alzheimer's disease.
Ledesma
M D
MD
Centro de Biología Molecular (CSIC-UAM), Universidad Autónoma, Madrid, Spain.
Correas
I
I
Avila
J
J
Díaz-Nido
J
J
D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002417:Cattle; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D016875:tau Proteins / Q000378:metabolism*
D016875:tau Proteins; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D016203:CDC2 Protein Kinase