Possible Involvement of Alzheimer Amyloid Precursor Protein and Its Associated Protein Kinase Activity in Signal Transduction Pathway (BIOORGANIC CHEMISTRY-Molecular Clinical Chemistry)

Abstract

Amyloid precursor protein (APP) is one of the major causative agents of Alzheimer's disease and possesses a receptor-like structure with extracellular, single transmembrane, and cytoplasmic domains. To explore the physiological significance of APP in the cell, we focuses on the possible involvement of APP in signal transduction pathways. Using affinity precipitation followed by an in vitro kinase assay, we found an APP-associated protein kinase activity in the cytosol/membrane fraction of human cell lines derived from neuroblastoma, glioblastoma, embryo, epidermis, and cervix cancer. The kinase was capable of phosphorylating APP- and/or kinase-associated cellular proteins and of binding to a part of the extracellular domain of APP. The kinase activity was specific for serine residues. These results suggest that APP may function in a form of heteromer with a membrane-spanning receptor-like kinase via binding to the extracellular domain characteristic of other receptor systems.