Phosphorylation of tau proteins to a state like that in Alzheimer's brain is catalyzed by a calcium/calmodulin-dependent kinase and modulated by phospholipids.
Calcium/calmodulin (CaM)-dependent protein kinases isolated from bovine and rat brains phosphorylate the microtubule-associated tau protein in the mode that shifts the mobility of tau in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (mode I). This mode of tau phosphorylation is the one that occurs abnormally in Alzheimer's lesions. Purified tau protein in solution can be phosphorylated by the Ca2+/CaM kinases maximally to about 50% of the total tau protein. Incorporation of one phosphate group per mol of tau is sufficient to shift the protein to a slower migrating electrophoretic band. Additional phosphate incorporation into the shifted tau proteins can occur depending on protein kinase concentration. In the presence of phosphatidylserine, tau proteins were phosphorylated to an extent of 100% at a tau: phosphatidylserine ratio of 20. Phosphatidylethanolamine also stimulated tau phosphorylation by Ca2+/CaM kinase and phosphatidylinositol was found to be a potent inhibitor of tau protein phosphorylation. The direct observation that tau proteins interact with phospholipids such as phosphatidylethanolamine and phosphatidylinositol, resulting in a smearing of the protein band on sodium dodecyl sulfate-gel electrophoresis, supports the possibility that tau protein may interact with phospholipid membranes in vivo and that tau protein phosphorylation could be modulated by the phospholipid composition of the membranes with which tau interacts.
D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D002417:Cattle; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010718:Phosphatidylserines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D016875:tau Proteins
D002147:Calmodulin; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D010718:Phosphatidylserines; D010743:Phospholipids; D016875:tau Proteins; D011494:Protein Kinases; D002118:Calcium