Document Detail

Integrin-linked kinase regulates the nuclear entry of the c-Jun coactivator alpha-NAC and its coactivation potency.
MedLine Citation:
PMID:  15299025     Owner:  NLM     Status:  MEDLINE    
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.
Isabelle Quélo; Claude Gauthier; Gregory E Hannigan; Shoukat Dedhar; René St-Arnaud
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-08-06
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  279     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-10-11     Completed Date:  2004-12-14     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  43893-9     Citation Subset:  IM    
Genetics Unit, Shriners Hospital for Children Montréal, Québec H3G 1A6, Canada.
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MeSH Terms
COS Cells
Cell Nucleus / enzymology*
Cercopithecus aethiops
DNA, Complementary / genetics
Molecular Chaperones
Phosphoserine / metabolism
Protein Transport / physiology
Protein-Serine-Threonine Kinases / metabolism*
Proto-Oncogene Proteins c-jun / metabolism
Recombinant Proteins / metabolism
Trans-Activators / metabolism*
Transcription, Genetic
Reg. No./Substance:
0/DNA, Complementary; 0/Molecular Chaperones; 0/Proto-Oncogene Proteins c-jun; 0/Recombinant Proteins; 0/Trans-Activators; 0/nascent-polypeptide-associated complex; 17885-08-4/Phosphoserine; EC 2.7.1.-/integrin-linked kinase; EC Kinases

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