Phosphorylation of thr668in the cytoplasmic domain of the Alzheimer's disease amyloid precursor protein by stress‐activated protein kinase 1b (Jun N‐terminal kinase‐3)
Open Access
- 1 January 2001
- journal article
- research article
- Published by Wiley in Journal of Neurochemistry
- Vol. 76 (1), 316-320
- https://doi.org/10.1046/j.1471-4159.2001.00102.x
Abstract
Threonine668 (thr668) within the carboxy‐terminus of the Alzheimer's disease amyloid precursor protein (APP) is a known in vivo phosphorylation site. Phosphorylation of APPthr668 is believed to regulate APP function and metabolism. Thr668 precedes a proline, which suggests that it is targeted for phosphorylation by proline‐directed kinase(s). We have investigated the ability of four major neuronally active proline‐directed kinases, cyclin dependent protein kinase‐5, glycogen synthase kinase‐3β, p42 mitogen‐activated protein kinase and stress‐activated protein kinase‐1b, to phosphorylate APPthr668 and report here that SAPK1b induces robust phosphorylation of this site both in vitro and in vivo. This finding provides a molecular framework to link cellular stresses with APP metabolism in both normal and disease states.Keywords
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