Serine 209 resides within a putative p38(MAPK) consensus motif and regulates monoamine oxidase-A activity.
J Neurochem
; 111(1): 101-10, 2009 Oct.
Article
em En
| MEDLINE
| ID: mdl-19650872
ABSTRACT
The p38 mitogen-activated protein kinase (MAPK) cascade as well as the enzyme monoamine oxidase-A (MAO-A) have both been associated with oxidative stress. We observed that the specific inhibition of the p38(MAPK) protein [using either a chemical inhibitor or a dominant-negative p38(MAPK) clone] selectively induces MAO-A activity and MAO-A-sensitive toxicity in several neuronal cell lines, including primary cortical neurons. Over-expression of a constitutively active p38(MAPK) results in the phosphorylation of the MAO-A protein and inhibition of MAO-A activity. The MAO-A(Ser209Glu) phosphomimic - bearing a targeted substitution within a putative p38(MAPK) consensus motif - is neither active nor neurotoxic. In contrast, the MAO-A(Ser209Ala) variant (mimics dephosphorylation) does not associate with p38(MAPK), and is both very active and very toxic. Substitution of the homologous serine in the MAO-B isoform, i.e. Ser200, with either Glu or Ala does not affect the catalytic activity of the corresponding over-expressed proteins. These combined in vitro data strongly suggest a direct p38(MAPK)-dependent inhibition of MAO-A function. Based on published observations, this endogenous means of selectively regulating MAO-A function could provide for an adaptive response to oxidative stress associated with disorders as diverse as depression, reperfusion/ischemia, and the early stages of Alzheimer's disease.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Serina
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Sequência Consenso
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Proteína Quinase 11 Ativada por Mitógeno
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Monoaminoxidase
Limite:
Animals
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Female
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Humans
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Pregnancy
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article