Characterization of mAb AP422, a novel phosphorylation-dependent monoclonal antibody against tau protein.
A monoclonal antibody (AP422) specific for phosphoserine 422 in microtubule-associated protein tau has been produced. It strongly labels paired helical filament (PHF) tau from Alzheimer's disease brain in a phosphorylation-dependent manner. By contrast, AP422 only labels a small fraction of fetal tau and a very small fraction of tau from adult brain. The amount of tau phosphorylated at Ser-422 in normal brain is minor relative to that phosphorylated at sites recognized by other phosphorylation-dependent anti-tau antibodies of known epitope. It follows that AP422 is the most specific anti-tau antibody available for detecting the neurofibrillary lesions of Alzheimer's disease. We also show that Ser-422 in tau is a good in vitro substrate for mitogen-activated protein kinase, but not for glycogen synthase kinase-3 or neuronal cdc2-like kinase.
Hasegawa
M
M
MRC Laboratory of Molecular Biology, Cambridge, UK.
Jakes
R
R
Crowther
R A
RA
Lee
V M
VM
Ihara
Y
Y
Goedert
M
M
D000544:Alzheimer Disease / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010748:Phosphopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology*; D010766:Phosphorylation; D010768:Phosphoserine; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D016875:tau Proteins / Q000032:analysis / Q000276:immunology* / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D010748:Phosphopeptides; D011994:Recombinant Proteins; D016875:tau Proteins; D010768:Phosphoserine