Abstract |
Hyperphosphorylation of the microtubule-associated protein tau is a characteristic of Alzheimer brain tissue. Recent in vitro data suggest that mitogen-activated protein kinase (MAPK), a proline-directed protein kinase, phosphorylates the sites on tau common to Alzheimer's disease. Using an okadaic acid-induced tau hyperphosphorylation model, we have tested the requirement for MAPK activity, using a specific inhibitor ¿PD098059 [2-(2'-amino-3'-methoxyphenyl)oxanaphthalen-4-one]¿ of the MAPK activator Mek1. Mobility shift, phosphoepitope analysis, and direct measurement of kinase activity indicated that the Mek1 inhibitor dose-dependently blocked basal and okadaic acid-induced MAPK activation. Despite a block of MAPK activation by this inhibitor, robust tau hyperphosphorylation was observed in response to okadaic acid. In addition, activation of MAPK by phorbol 12-myristate 13-acetate did not result in tau phosphorylation, indicating that in primary cultures of cortical neurons elevated MAPK activity is not sufficient to induce tau hyperphosphorylation.
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Authors | D T Ho, H Shayan, T H Murphy |
Journal | Journal of neurochemistry
(J Neurochem)
Vol. 68
Issue 1
Pg. 106-11
(Jan 1997)
ISSN: 0022-3042 [Print] England |
PMID | 8978715
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Enzyme Inhibitors
- Flavonoids
- tau Proteins
- Okadaic Acid
- Calcium-Calmodulin-Dependent Protein Kinases
- Tetradecanoylphorbol Acetate
- 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
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Topics |
- Animals
- Calcium-Calmodulin-Dependent Protein Kinases
(metabolism)
- Cells, Cultured
- Cerebral Cortex
(cytology, metabolism)
- Dose-Response Relationship, Drug
- Enzyme Activation
(drug effects)
- Enzyme Inhibitors
(pharmacology)
- Flavonoids
(pharmacology)
- Neuroglia
(metabolism)
- Neurons
(metabolism)
- Okadaic Acid
(pharmacology)
- Phosphorylation
(drug effects)
- Rats
(embryology)
- Tetradecanoylphorbol Acetate
(pharmacology)
- tau Proteins
(metabolism)
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