Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10636 (tau protein)
 5,110 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In Alzheimer's disease, paired helical filaments composed mainly of abnormally phosphorylated tau accumulate in certain selected neurons of the brain, and microtubules are rarely seen in the affected cells. In the present study, the binding of 32P-labeled 8-azidoguanosine triphosphate ([gamma-32P]8N3GTP), the photoaffinity analogue of GTP to the beta-subunit of tubulin in brain homogenates was found to be markedly lower in patients with Alzheimer's disease than in aged control human cases. No significant differences were observed in the levels of the alpha- and beta-subunits of tubulin between Alzheimer's disease and control brains obtained 2-7 h postmortem. In nine of 19 Alzheimer's disease and 11 of 12 control autopsied brains (2-7 h postmortem and stored at -75 degrees C) tubulin was isolated successfully from brain cytosol by in vitro polymerization induced with DEAE-dextran. The GTP binding was observed in the two cycled assembled microtubule preparations from all the normal control, and in eight of nine Alzheimer's disease cases. Alzheimer's disease microtubule preparations contained varying amounts of abnormally phosphorylated tau, whereas no abnormal tau was detected in the control brain preparations. Addition of bovine tau to bovine, normal human, and Alzheimer's disease brain tubulin preparations markedly increased GTP binding to the beta-subunit. An alkaline phosphatase-treated paired helical filament-enriched preparation increased by approximately twofold the GTP binding to bovine brain tubulin. GTP binding to tubulin prepared by phosphocellulose chromatography of two cycled microtubules from three Alzheimer's disease and three normal control brains, revealed insignificant differences between the two groups. These findings have suggested that (1) tau protein promotes the GTP binding to the beta-subunit of tubulin, and (2) the breakdown of the microtubule system in brains of patients with Alzheimer's disease might in part be due to the abnormal phosphorylation of tau which depresses the GTP binding.
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PMID:Guanosine triphosphate binding to beta-subunit of tubulin in Alzheimer's disease brain: role of microtubule-associated protein tau. 783 71

Phosphorylation is an indispensable process for energy and signal transduction in biological systems. AlCl3 at 10 nM to 10 microM range activated in-vitro [gamma-32P]ATP phosphorylation of the brain (tau) tau protein in both normal human or E. coli expressed tau forms; in the presence of the kinases P34, PKP, and PKC. However, higher concentrations of ALCl3 inhibited the tau phosphorylation with P34, PKP, and PKC to a maximum at 1 mM level. AlCl3 at 100 microM to 500 microM range induced non-enzymatic phosphorylation of tau with gamma-ATP, gamma-GTP, and alpha-GTP. AlCl3 activated histone phosphorylation by P34 in a similar pattern. The hyperphosphorylation of tau by Al3+ was accompanied by molecular shift and mobility retardation in SDS-PAGE. This may demonstrate the mechanism of the longterm neurological effect of Al3+ in human brain leading to the formation of the neurofibrillary tangles related to Alzheimer's disease.
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PMID:Aluminum interaction with human brain tau protein phosphorylation by various kinases. 827 Jul 65

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.
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PMID:Aluminum-induced nonenzymatic phospho-incorporation into human tau and other proteins. 850 22

Microtubules are designed to be dynamically unstable. GTP hydrolysis converts an initially stable polymeric structure into an unstable one in which strain at the interfaces between longitudinal neighbours in the helical lattice of subunits is balanced by lateral interactions. However, stability can be modulated by a variety of factors, including associated proteins and a variety of drug molecules. Stabilising drugs such as Taxol and the assembly-promoting repeat motifs of tau protein occupy a special pocket in beta-tubulin. Microtubule destabilizing drugs such as colchicine alter the longitudinal interfaces of the subunits so that they cannot assemble into a microtubule lattice. These mechanisms are discussed in terms of the atomic structure of the protein.
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PMID:Microtubule structure and its stabilisation. 1528 Sep 46