Drastic reduction of the zinc‐ and magnesium‐stimulated protein tyrosine kinase activities in Alzheimer's disease hippocampus

Abstract

Tyrosine phosphorylation of proteins from postmortem hippocampi of five Alzheimer's disease and five control cases have been compared. It was found that addition of Zn2+ or Mg2+ to membrane fractions of control hippocampi caused the phosphorylation of 32-, 40-, 55-, 60-, 80- and 100-kDa proteins or 43-, 55-, 60- and 90-KdA proteins, respectively. The phosphorylation of all these proteins is shown to be drastically reduced in Alzheimer's disease hippocampi. Vanadate, an inhibitor of protein tyrosine phosphatases, had no influence on the level of protein phosphorylation. Western blot analysis did not reveal any differences in the anti-phosphotyrosine immunoreactive membrane proteins from Alzheimer's disease and control hippocampi. Tyrosine kinase activity of immunoprecipitated p60c-src from Alzheimer's disease and control hippocampi were the same. In conclusion, the Zn(2+)- and Mg(2+)-stimulated tyrosine kinase activities, distinct from activity of p60c-src, are decreased in Alzheimer's disease hippocampus.