Elevated amyloid beta protein(1-40) level induces CREB phosphorylation at serine-133 via p44/42 MAP kinase (Erk1/2)-dependent pathway in rat pheochromocytoma PC12 cells

N Sato; K Kamino; K Tateishi; T Satoh; Y Nishiwaki; A Yoshiiwa; T Miki; T Ogihara

doi:10.1006/bbrc.1997.6341

Elevated amyloid beta protein(1-40) level induces CREB phosphorylation at serine-133 via p44/42 MAP kinase (Erk1/2)-dependent pathway in rat pheochromocytoma PC12 cells

Biochem Biophys Res Commun. 1997 Mar 27;232(3):637-42. doi: 10.1006/bbrc.1997.6341.

Authors

N Sato¹, K Kamino, K Tateishi, T Satoh, Y Nishiwaki, A Yoshiiwa, T Miki, T Ogihara

Affiliation

¹ Department of Geriatric Medicine, Osaka University Medical School, Japan.

PMID: 9126327
DOI: 10.1006/bbrc.1997.6341

Abstract

The deposition of amyloid beta protein (A beta) in the cerebral cortex is the pathological characteristic of Alzheimer's disease (AD), and patients with AD suffer from progressive memory loss. Transgenic experiments have revealed that long-term memory is dependent on cyclic AMP-response element binding protein, CREB. CREB phosphorylation at serine-133 is essential for its transcriptional activity. Here we demonstrated that A beta(1-40), at a concentration more than 1 microM, induced CREB phosphorylation at serine-133 in rat pheochromocytoma PC12 cells. A beta(1-40) induced phosphorylation of p44 and p42 MAP kinases (Erk1 and Erk2) at tyrosine-204, and PD98059, a MEK1 inhibitor, inhibited A beta(1-40)-induced CREB phosphorylation at serine-133. We conclude that elevated A beta(1-40) level induces CREB phosphorylation at serine-133 via p44/42 MAP kinase-dependent pathway.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amyloid beta-Peptides / metabolism*
Animals
Binding Sites
Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
Cyclic AMP Response Element-Binding Protein / chemistry
Cyclic AMP Response Element-Binding Protein / metabolism*
Enzyme Inhibitors / pharmacology
Flavonoids / pharmacology
Kinetics
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases*
PC12 Cells
Peptide Fragments / metabolism*
Phosphorylation
Protein-Tyrosine Kinases / antagonists & inhibitors
Protein-Tyrosine Kinases / metabolism*
Rats
Serine / chemistry

Substances

Amyloid beta-Peptides
Cyclic AMP Response Element-Binding Protein
Enzyme Inhibitors
Flavonoids
Peptide Fragments
amyloid beta-protein (1-40)
Serine
Protein-Tyrosine Kinases
Calcium-Calmodulin-Dependent Protein Kinases
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one