Microtubule-associated protein tau is phosphorylated by protein kinase C on its tubulin binding domain.
We have analyzed the in vitro phosphorylation of tau protein by Ca2+/calmodulin-dependent protein kinase, casein kinase II, and proline-directed serine/threonine protein kinase. These kinases phosphorylate tau protein in sites localized in different regions of the molecule, as determined by peptide mapping analyses. Focusing on the phosphorylation of tau by protein kinase C, it was calculated as an incorporation of 4 mol of phosphate/mol of tau. Limited proteolysis assays suggest that the phosphorylation sites could be located within the tubulin-binding domain. Direct phosphorylation of synthetic peptides corresponding to the cysteine-containing tubulin-binding region present in both fetal and adult tau isoforms demonstrates that serine 313 is modified by protein kinase C. Phosphorylation of the synthetic peptide by protein kinase C diminishes its binding to tubulin, as compared with the unphosphorylated peptide.
Correas
I
I
Centro de Biología Molecular, Facultad de Ciencias, Universidad Autónoma, Madrid, Spain.
Díaz-Nido
J
J
Avila
J
J
D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D047388:Casein Kinases; D002417:Cattle; D004591:Electrophoresis, Polyacrylamide Gel; D007700:Kinetics; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000302:isolation & purification; D010748:Phosphopeptides / Q000302:isolation & purification; D010750:Phosphoproteins / Q000302:isolation & purification; D010761:Phosphorus Radioisotopes; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D013379:Substrate Specificity; D014404:Tubulin / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
D010446:Peptide Fragments; D010748:Phosphopeptides; D010750:Phosphoproteins; D010761:Phosphorus Radioisotopes; D014404:Tubulin; D016875:tau Proteins; D000255:Adenosine Triphosphate; D011494:Protein Kinases; D047388:Casein Kinases; D011493:Protein Kinase C