Protein kinase Akt/PKB phosphorylates heme oxygenase-1 in vitro and in vivo.
FEBS Lett
; 578(1-2): 90-4, 2004 Dec 03.
Article
em En
| MEDLINE
| ID: mdl-15581622
ABSTRACT
Heme oxygenase-1 (HO-1) is a stress response protein that protects cells against diverse noxious stimuli. Although regulation of HO-1 occurs mainly at the transcriptional level, its posttranslational modifications remain unexplored. We have identified a putative consensus sequence for phosphorylation by Akt/PKB of HO-1 at Ser188. Recombinant human and rat HO-1, but not mutant HO-1(S188A), are phosphorylated in vitro by Akt/PKB. Isotopic 32P-labeling of HEK293T cells confirmed that HO-1 is a phosphoprotein and that the basal HO-1 phosphorylation is increased by Akt1 activation. HO-1(S188D), a single point mutant equivalent to the phosphorylated protein, exhibited over 1.6-fold higher activity than wild type HO-1. Fluorescence resonance energy transfer (FRET) studies indicated that HO-1(S188D) bound to cytochrome P450 reductase (CPR) and biliverdin reductase (BVR) with a slightly lower Kd than wild-type HO-1. Although the changes in activity are small, this study provides the first evidence for a role of the survival kinase Akt in the regulation of HO-1.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sistemas do Segundo Mensageiro
/
Regulação Enzimológica da Expressão Gênica
/
Proteínas Proto-Oncogênicas
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Proteínas Serina-Treonina Quinases
/
Heme Oxigenase (Desciclizante)
Limite:
Animals
/
Humans
Idioma:
En
Revista:
FEBS Lett
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Espanha