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.
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.
Sato
N
N
Department of Geriatric Medicine, Osaka University Medical School, Japan.
Kamino
K
K
Tateishi
K
K
Satoh
T
T
Nishiwaki
Y
Y
Yoshiiwa
A
A
Miki
T
T
Ogihara
T
T
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D007700:Kinetics; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D016716:PC12 Cells; D010446:Peptide Fragments / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D012694:Serine / Q000737:chemistry
D016229:Amyloid beta-Peptides; D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D005419:Flavonoids; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D012694:Serine; D011505:Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one