CELL-SURFACE RECEPTOR FUNCTION OF AMYLOID PRECURSOR PROTEIN THAT ACTIVATES SER THR KINASES/

Amyloid precursor protein (APP) has been shown to serve as a G(o)-coup led receptor in cell-free systems [Okamoto et al: J Biol Chem 1995;270 :4205-4208], However, it has not been known whether APP exerts intrace llular signaling functions in living cells. In this study, we show tha t stimulation of APP by anti-APP antibody as well as by a mutation fou nd in familial Alzheimer's disease results in activation of a specific set of mitogen-activated protein kinases in multiple vertebrate cells . We conclude that APP acts as a cell surface receptor of biological r elevance that turns on specific Ser/Thr kinases, and suggest that the signaling function of APP is a potential target of familial Alzheimer' s disease mutations.