PKA, PKC, and the protein phosphatase 2A influence HAND factor function: a mechanism for tissue-specific transcriptional regulation.
Mol Cell
; 12(5): 1225-37, 2003 Nov.
Article
em En
| MEDLINE
| ID: mdl-14636580
ABSTRACT
The bHLH factors HAND1 and HAND2 are required for heart, vascular, neuronal, limb, and extraembryonic development. Unlike most bHLH proteins, HAND factors exhibit promiscuous dimerization properties. We report that phosphorylation/dephosphorylation via PKA, PKC, and a specific heterotrimeric protein phosphatase 2A (PP2A) modulates HAND function. The PP2A targeting-subunit B56delta specifically interacts with HAND1 and -2, but not other bHLH proteins. PKA and PKC phosphorylate HAND proteins in vivo, and only B56delta-containing PP2A complexes reduce levels of HAND1 phosphorylation. During RCHOI trophoblast stem cell differentiation, B56delta expression is downregulated and HAND1 phosphorylation increases. Mutations in phosphorylated residues result in altered HAND1 dimerization and biological function. Taken together, these results suggest that site-specific phosphorylation regulates HAND factor functional specificity.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Transcrição Gênica
/
Proteína Quinase C
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Proteínas Quinases Dependentes de AMP Cíclico
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Fosfoproteínas Fosfatases
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Regulação da Expressão Gênica no Desenvolvimento
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Subunidades Proteicas
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Proteínas de Ligação a DNA
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article