PT - JOURNAL ARTICLE AU - A. Mudher AU - S. Chapman AU - J. Richardson AU - A. Asuni AU - G. Gibb AU - C. Pollard AU - R. Killick AU - T. Iqbal AU - L. Raymond AU - I. Varndell AU - P. Sheppard AU - A. Makoff AU - E. Gower AU - P. E. Soden AU - P. Lewis AU - M. Murphy AU - T. E. Golde AU - H. T. Rupniak AU - B. H. Anderton AU - S. Lovestone TI - Dishevelled Regulates the Metabolism of Amyloid Precursor Protein via Protein Kinase C/Mitogen-Activated Protein Kinase and c-Jun Terminal Kinase AID - 10.1523/JNEUROSCI.21-14-04987.2001 DP - 2001 Jul 15 TA - The Journal of Neuroscience PG - 4987--4995 VI - 21 IP - 14 4099 - http://www.jneurosci.org/content/21/14/4987.short 4100 - http://www.jneurosci.org/content/21/14/4987.full SO - J. Neurosci.2001 Jul 15; 21 AB - Alzheimer's disease (AD) is a disorder of two pathologies: amyloid plaques, the core of which is a peptide derived from the amyloid precursor protein (APP), and neurofibrillary tangles composed of highly phosphorylated tau. Protein kinase C (PKC) is known to increase non-amyloidogenic α-secretase cleavage of APP, producing secreted APP (sAPPα), and glycogen synthase kinase (GSK)-3β is known to increase tau phosphorylation. Both PKC and GSK-3β are components of the wnt signaling cascade. Here we demonstrate that overexpression of another member of this pathway, dishevelled (dvl-1), increases sAPPα production. The dishevelled action on APP is mediated via both c-jun terminal kinase (JNK) and protein kinase C (PKC)/mitogen-activated protein (MAP) kinase but not via p38 MAP kinase. These data position dvl-1 upstream of both PKC and JNK, thereby explaining the previously observed dual signaling action of dvl-1. Furthermore, we show that human dvl-1 and wnt-1 also reduce the phosphorylation of tau by GSK-3β. Therefore, both APP metabolism and tau phosphorylation are potentially linked through wnt signaling.