Cell-extracellular matrix interactions stimulate the AP-1 transcription factor in an integrin-linked kinase- and glycogen synthase kinase 3-dependentmanner

Citation
Aa. Troussard et al., Cell-extracellular matrix interactions stimulate the AP-1 transcription factor in an integrin-linked kinase- and glycogen synthase kinase 3-dependentmanner, MOL CELL B, 19(11), 1999, pp. 7420-7427
Citations number
50
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
MOLECULAR AND CELLULAR BIOLOGY
ISSN journal
0270-7306 → ACNP
Volume
19
Issue
11
Year of publication
1999
Pages
7420 - 7427
Database
ISI
SICI code
0270-7306(199911)19:11<7420:CMISTA>2.0.ZU;2-#
Abstract
Integrin-mediated interactions of cells with components of the extracellula r matrix regulate cell survival, cell proliferation, cell differentiation, and cell migration. Some of these physiological responses are regulated via activation of transcription factors such as activator protein 1 (AP-1). In tegrin-linked kinase (ILK) is an ankyrin repeat containing serine-threonine protein kinase whose activity is rapidly and transiently stimulated by cel l-fibronectin interactions as well as by insulin stimulation. ILK activates protein kinase B and inhibits the glycogen synthase kinase 3 (GSK-3) activ ity in a phosphatidylinositol-3-kinase (PI 3-kinase)-dependent manner, We n ow show that cell adhesion to fibronectin results in a rapid and transient stimulation of AP-1 activity. At the same time, the kinase: activity of ILK is stimulated whereas that of GSK-3 is inhibited. This fibronectin-depende nt activation of AP-1 activity is inhibited in a dose-dependent manner if t he cells are transfected with wild-type GSK-3, and also by inhibitors of PI 3-kinase. Stable or transient overexpression of ILK results in a stimulati on of AP-1 activity which is inhibited by cotransfection with wild-type GSK -3 and kinase-deficient ILK. Transient transfection of ILK in HEK-293 cells stimulates complex formation between an AP-1 consensus oligonucleotide and nuclear proteins containing c-jun, The formation of this complex is inhibi ted by cotransfection with active GSK-3 or kinase-deficient ILK, suggesting that ILK may regulate AP-1 activation by inhibiting GSK-3, which has previ ously been shown to be a negative regulator of AP-1, In the presence of ser um, ILK has no effect on the phosphorylation of Ser-73 in the N-terminal tr ansactivation domain of c-jun, These results demonstrate a novel signaling pathway for the adhesion-mediated stimulation of AP-1 transcriptional activ ity involving ILK and GSK-3 and the subsequent regulation of the c-jun-DNA interaction.