Integrin-linked kinase regulates the nuclear entry of the c-Jun coactivator alpha-NAC and its coactivation potency.
J Biol Chem
; 279(42): 43893-9, 2004 Oct 15.
Article
em En
| MEDLINE
| ID: mdl-15299025
ABSTRACT
Overexpression of the integrin-linked kinase (ILK) was shown to increase c-Jun-dependent transcription. We now show that this effect of ILK involves the c-Jun transcriptional coactivator, nascent polypeptide-associated complex and coactivator alpha (alpha-NAC). ILK phosphorylated alpha-NAC on residue Ser-43 upon adhesion of cells to fibronectin. Co-expression of constitutively active ILK with alpha-NAC led to the nuclear accumulation of the coactivator. Conversely, alpha-NAC remained in the cytoplasm of cells transfected with a dominant-negative ILK mutant, and a mutated alpha-NAC at phosphoacceptor position Ser-43 (S43A) also localized outside of the nucleus. The S43A alpha-NAC mutant could not potentiate the effect of ILK on c-Jun-dependent transcription. We conclude that ILK-dependent phosphorylation of alpha-NAC induced the nuclear accumulation of the coactivator and that phosphorylation of alpha-NAC by ILK is required for the potentiation of c-Jun-mediated responses by the kinase. The results represent one of the rare examples of a transcriptional coactivator shuttling between the cytosol and the nucleus.
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Base de dados:
MEDLINE
Assunto principal:
Transativadores
/
Núcleo Celular
/
Proteínas Serina-Treonina Quinases
Limite:
Animals
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article