p493F12 kinase: a novel MAP kinase expressed in a subset of neurons in the human nervous system

Abstract

Monoclonal antibody 3F12 identifies a cytoplasmic antigen of 49 kDa in human hippocampus and neocortex. The distribution of 3F12 immunoreactive neurons closely matches that of Alzheimer's disease (AD) targeted neurons in these areas. In some hippocampal neurons of AD patients, this antigen colocalizes with ALZ-50, indicating the presence of AD pathology in these neurons. Molecular characterization of the 3F12 cDNA revealed it to be a member of the MAP kinase family, showing 43% amino acid sequence identity to human extracellular related kinase 2 (p42mapk). We have confirmed that p493F12 kinase autophosphorylates both threonine and tyrosine residues, as expected for a MAP kinase. The p49 mRNA is expressed exclusively in the nervous system. In the brain, the distribution of these neurons closely corresponds to 3F12 antigen-bearing neurons. The p493F12 gene maps to the human chromosome 21q21 region, a region that may be important in the pathogenesis of AD and Down's syndrome.