Binding specificity of monoclonal antibody AD2: influence of the phosphorylation state of tau.
Using recombinant human tau protein phosphorylated by a brain extract and the glycogen synthase kinase-3beta in the absence or the presence of heparin, we showed that phosphorylation-dependent antibody AD2 recognition only requires phosphorylated Ser-396. By the Spot multiple peptide synthesis method, we showed that Tyr-394, Ser(P)-396 and Pro-397 are critical for AD2 binding. A decrease in the binding of AD2 was observed with increasing phosphorylation of residues in the vicinity of Ser(P)-396.
Torreilles
F
F
CNRS UMR 5094 Institut de Biotechnologie en Immunoanalyse et Pharmacologie UFR Pharmacie, 15 Av. Charles Flahault, 34060 Montpellier Cedex 2, France.
Roquet
F
F
Granier
C
C
Pau
B
B
Mourton-Gilles
C
C
D000544:Alzheimer Disease / Q000378:metabolism; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D000925:Anticoagulants / Q000494:pharmacology; D001923:Brain Chemistry; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D009474:Neurons / Q000737:chemistry / Q000201:enzymology; D010766:Phosphorylation; D011485:Protein Binding / Q000187:drug effects / Q000276:immunology; D016875:tau Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D016875:tau Proteins; D006493:Heparin; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3