Aluminum-induced nonenzymatic phospho-incorporation into human tau and other proteins.
Incubation of purified recombinant human tau protein with aluminum salts at concentrations > or = 100 microM induces aggregation of tau that prevents its entry into SDS-polyacrylamide gels and filtration through nylon membranes. This effect is noncovalent and can be reversed by addition of EDTA. However, when incubated along with ATP, GTP, or CTP, aluminum catalyzes a covalent linkage that results in incorporation of the alpha- and gamma-phosphates into the tau protein (phospho-incorporation). The sensitivity to phosphatases and partial hydrolysis and the labeling observed with ATP containing radioisotopes at different positions suggest a novel reaction in which the entire triphosphate moiety is transferred from ATP and linked to tau via an O-linkage to the alpha-phosphate. The aggregation and triphosphorylation phenomena were not catalyzed by divalent or quadrivalent cations, but similar effects were observed with some other trivalent cations. They occurred at aluminum concentrations similar to those found in human brains with Alzheimer's disease, suggesting the possibility that related reactions may have physiological significance in vivo.
Section of Biochemistry, Molecular and Cell Biology, Cornell University, Ithaca, New York 14853.
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Abdel-Ghany
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el-Sebae
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Shalloway
D000255:Adenosine Triphosphate / Q000378:metabolism; D000535:Aluminum / Q000494:pharmacology*; D000077410:Aluminum Chloride; D017607:Aluminum Compounds; D002364:Caseins / Q000378:metabolism; D002712:Chlorides / Q000494:pharmacology*; D004492:Edetic Acid / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007700:Kinetics; D008970:Molecular Weight; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism; D015032:Zinc / Q000378:metabolism*; D016875:tau Proteins / Q000302:isolation & purification / Q000378:metabolism*
D017607:Aluminum Compounds; D002364:Caseins; D002712:Chlorides; D011994:Recombinant Proteins; D012709:Serum Albumin; D016875:tau Proteins; D000077410:Aluminum Chloride; D000255:Adenosine Triphosphate; D004492:Edetic Acid; D000535:Aluminum; D010751:Phosphopyruvate Hydratase; D015032:Zinc