抄録
Recent studies in Alzheimer brains have shown aberrant protein phosphorylation, suggesting an alteration in protein kinases and/or phosphoprotein phosphatases. The separation profile on Sephadex G-100 gel filtration chromatography revealed that two major forms of high-molecular-weight (HMW) and low-molecular-weight (LMW) acid phosphatase were present in the crude extracts of human brains. In Alzheimer brains, the LMW acid phosphatase activity was significantly decreased compared to that in control brains. A specific antibody was prepared to analyze the protein level of this enzyme. Western blot analysis indicated that the level of LMW acid phosphatase protein was significantly reduced, whereas the activity of LMW acid phosphatase per enzyme molecule was not changed in Alzheimer brains. These results suggest that the reduction of LMW acid phosphatase activity in Alzheimer brains is due to its decreased protein level in Alzheimer's disease. The endogenous substrate of LMW acid phosphatase in the brain was also investigated. LMW acid phosphatase was purified from bovine brain with a molecular mass of 17 kDa. The LMW acid phosphatase from bovine brain dephosphorylated a Mr. 170 kDa phosphotyrosine protein in rat brain extracts. This Mr. 170 kDa protein was considered to be the epidermal growth factor (EGF) receptor using a specific antibody. These results suggest that LMW acid phosphatase in the brain may regulate EGF receptor-dependent transmembrane signalling by dephosphorylating the phosphorylated receptor.
