AMYLOID PRECURSOR PROTEIN ACTIVATES PHOSPHOTYROSINE SIGNALING PATHWAY

Amyloid precursor protein (APP) is known to have neurotrophic effects but little information is available on the signaling pathways activate d by APP. Since neurotrophic factors activate tyrosine phosphorylation signaling pathway in general, we investigated whether or not APP acti vates tyrosine phosphorylation pathway. alpha-Secretase derived APP (s APP alpha) increased the number of neurites per cell and enhanced tyro sine phosphorylation levels on distinct 125 and 200 kDa protein bands. The APP3 19-335 17-mer peptide, which has been reported to be respons ible for the neurotrophic effect of sAPP alpha [Jin, L.-W., Ninomiya, H., Roch, J.-M., Schubert, D., Masliah, E., Otero, D.A.C. and Saitoh, T., J. Neurosci., 14 (1994) 5461-5470], increased neurite extension as well as tyrosine phosphorylation on 125 and 200 kDa proteins in a sim ilar manner to sAPP alpha. Both effects were blocked by an antagonist peptide to 17-mer ERMSQ (APP329-333). These results indicate that the 17-mer domain of APP induces tyrosine phosphorylation on distinct prot eins under the condition that induces neurite extension. (C) 1997 Else vier Science Ireland Ltd.