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• W2051222628 endingPage "14162" @default.
• W2051222628 startingPage "14156" @default.
• W2051222628 abstract "The modulation of the activity of mitogen-activated protein kinase (MAPK) by endogenous growth factors or growth inhibitors provides a potential means of regulating cell proliferation. We determined the effect of the endogenous anti-proliferative peptide, atrial natriuretic peptide (ANP), on the ability of MAPK to phosphorylate myelin basic protein. In astrocytes, MAPK activity was significantly stimulated (up to 3-fold) by three known glial mitogens, endothelin-3, platelet-derived growth factor, or phorbol 12-myristate 13-acetate. ANP inhibited by 55–70% the ability of each of these mitogens to activate MAPK. The effects of ANP were equipotent to those caused by C-ANP 4–23, a peptide that specifically binds to the natriuretic peptide clearance receptor. Additionally, both natriuretic peptides caused a 70–80% inhibition of the sodium vanadate-stimulated MAPK activity, complete inhibition of the okadaic acid-stimulated activity, and inhibition of the mitogen-stimulated phosphorylation of MAPK. To understand the potential mechanism by which the natriuretic peptides act, we found that both ANP and C-ANP inhibited the mitogen-stimulated activity of the immediate upstream kinase in the cascade, MAPK kinase (MEK). C-ANP also strongly inhibited the endothelin-3-, platelet-derived growth factor-, and phorbol 12-myristate 13-acetate-induced stimulation of DNA synthesis in the astrocytes, while both okadaic acid and sodium vanadate significantly reversed these anti-proliferative actions. Our results identify ANP as a peptide hormone that inhibits growth factor-stimulated MAPK. These data suggest that the ability of the natriuretic peptides to inhibit MAPK may be important for their anti-growth actions. This effect likely occurs via the inhibition of upstream kinase(s), including MEK, uniquely resulting from ligand binding to the natriuretic peptide clearance receptor." @default.
• W2051222628 created "2016-06-24" @default.
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• W2051222628 date "1996-06-01" @default.
• W2051222628 modified "2023-10-18" @default.
• W2051222628 title "Atrial Natriuretic Peptide Inhibits Mitogen-activated Protein Kinase through the Clearance Receptor" @default.
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• W2051222628 doi "https://doi.org/10.1074/jbc.271.24.14156" @default.
• W2051222628 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/8662898" @default.
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