Abstract
Threonine(668) (thr(668)) within the carboxy-terminus of the Alzheimer's disease amyloid precursor protein (APP) is a known in vivo phosphorylation site. Phosphorylation of APPthr(668) is believed to regulate APP function and metabolism. Thr(668) 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-3 beta, p42 mitogen-activated protein kinase and stress-activated protein kinase-1b, to phosphorylate APPthr(668) 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alzheimer Disease / metabolism*
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Amyloid beta-Protein Precursor / metabolism*
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Animals
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Binding Sites / physiology
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CHO Cells
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COS Cells
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Calcium-Calmodulin-Dependent Protein Kinases / genetics
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Cricetinae
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Cyclin-Dependent Kinase 5
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Cyclin-Dependent Kinases / genetics
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Cyclin-Dependent Kinases / metabolism
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Glycogen Synthase Kinase 3
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Glycogen Synthase Kinases
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Isoenzymes / genetics
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Isoenzymes / metabolism
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Mitogen-Activated Protein Kinase 1 / genetics
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 10
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Mitogen-Activated Protein Kinases / genetics
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Mitogen-Activated Protein Kinases / metabolism*
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Neurofilament Proteins / metabolism
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Phosphorylation
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Protein Structure, Tertiary
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / metabolism*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Threonine / metabolism
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Transfection
Substances
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Amyloid beta-Protein Precursor
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Isoenzymes
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Neurofilament Proteins
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Recombinant Fusion Proteins
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neurofilament protein H
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Threonine
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Mitogen-Activated Protein Kinase 10
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Protein-Tyrosine Kinases
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Glycogen Synthase Kinases
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Cyclin-Dependent Kinase 5
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Calcium-Calmodulin-Dependent Protein Kinases
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Cyclin-Dependent Kinases
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinases
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Glycogen Synthase Kinase 3