Phosphorylation of more than one site is required for tight interaction of human tau protein with 14-3-3zeta. 2009

Nikolai N Sluchanko, and Alim S Seit-Nebi, and Nikolai B Gusev
Department of Biochemistry, School of Biology, M.V. Lomonosov Moscow State University, Moscow, Russian Federation.

Serine residues phosphorylated by protein kinase A (PKA) in the shortest isoform of human tau protein (tau3) were sequentially replaced by alanine and interaction of phosphorylated tau3 and its mutants with 14-3-3 was investigated. Mutation S156A slightly decreased interaction of phosphorylated tau3 with 14-3-3. Double mutations S156A/S267A and especially S156A/S235A, strongly inhibited interaction of phosphorylated tau3 with 14-3-3. Thus, two sites located in the Pro-rich region and in the pseudo repeats of tau3 are involved in phosphorylation-dependent interaction of tau3 with 14-3-3. The state of tau3 phosphorylation affects the mode of 14-3-3 binding and by this means might modify tau filament formation.

UI MeSH Term Description Entries
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012694 Serine A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids. L-Serine,L Serine
D016875 tau Proteins Microtubule-associated proteins that are mainly expressed in neurons. Tau proteins constitute several isoforms and play an important role in the assembly of tubulin monomers into microtubules and in maintaining the cytoskeleton and axonal transport. Aggregation of specific sets of tau proteins in filamentous inclusions is the common feature of intraneuronal and glial fibrillar lesions (NEUROFIBRILLARY TANGLES; NEUROPIL THREADS) in numerous neurodegenerative disorders (ALZHEIMER DISEASE; TAUOPATHIES). tau Protein,Protein, tau,Proteins, tau
D017354 Point Mutation A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. Mutation, Point,Mutations, Point,Point Mutations
D048948 14-3-3 Proteins A large family of signal-transducing adaptor proteins present in wide variety of eukaryotes. They are PHOSPHOSERINE and PHOSPHOTHREONINE binding proteins involved in important cellular processes including SIGNAL TRANSDUCTION; CELL CYCLE control; APOPTOSIS; and cellular stress responses. 14-3-3 proteins function by interacting with other signal-transducing proteins and effecting changes in their enzymatic activity and subcellular localization. The name 14-3-3 derives from numerical designations used in the original fractionation patterns of the proteins. 14-3-3 Protein,14-3-3 Protein, beta Isoform,14-3-3 Protein, epsilon Isoform,14-3-3 Protein, eta Isoform,14-3-3 Protein, gamma Isoform,14-3-3 Protein, tau Isoform,14-3-3 Protein, zeta Isoform,14-3-3 beta Protein,14-3-3 epsilon Protein,14-3-3 eta Protein,14-3-3 gamma Protein,14-3-3 tau Protein,14-3-3 zeta Protein,14-3-3beta Protein,14-3-3epsilon Protein,14-3-3eta Protein,14-3-3gamma Protein,14-3-3tau Protein,14-3-3zeta Protein,Brain 14-3-3 Protein,Protein 14-3-3,14 3 3 Protein,14 3 3 Protein, beta Isoform,14 3 3 Protein, epsilon Isoform,14 3 3 Protein, eta Isoform,14 3 3 Protein, gamma Isoform,14 3 3 Protein, tau Isoform,14 3 3 Protein, zeta Isoform,14 3 3 Proteins,14 3 3 beta Protein,14 3 3 epsilon Protein,14 3 3 eta Protein,14 3 3 gamma Protein,14 3 3 tau Protein,14 3 3 zeta Protein,14 3 3beta Protein,14 3 3epsilon Protein,14 3 3eta Protein,14 3 3gamma Protein,14 3 3tau Protein,14 3 3zeta Protein,14-3-3 Protein, Brain,Brain 14 3 3 Protein,Protein, 14-3-3tau,eta Protein, 14-3-3
D017868 Cyclic AMP-Dependent Protein Kinases A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition. Adenosine Cyclic Monophosphate-Dependent Protein Kinases,Protein Kinase A,cAMP Protein Kinase,cAMP-Dependent Protein Kinases,Cyclic AMP-Dependent Protein Kinase,cAMP-Dependent Protein Kinase,Adenosine Cyclic Monophosphate Dependent Protein Kinases,Cyclic AMP Dependent Protein Kinase,Cyclic AMP Dependent Protein Kinases,Protein Kinase, cAMP,Protein Kinase, cAMP-Dependent,Protein Kinases, cAMP-Dependent,cAMP Dependent Protein Kinase,cAMP Dependent Protein Kinases
D020033 Protein Isoforms Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING. Isoform,Isoforms,Protein Isoform,Protein Splice Variant,Splice Variants, Protein,Protein Splice Variants,Isoform, Protein,Isoforms, Protein,Splice Variant, Protein,Variant, Protein Splice,Variants, Protein Splice

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