Cell Adhesion

Cell adhesion: Linking Fibronectin Interaction to Transcription

Science's STKE  09 Nov 1999:
Vol. 1999, Issue 7, pp. tw2
DOI: 10.1126/stke.1999.7.tw2

Integrin-mediated cell adhesion is known to regulate gene expression through the activation of the transcription factor AP-1. Troussard et al. show that this event does indeed occur when cells interact with the extracellular matrix component fibronectin (FN). Based on earlier evidence that FN stimulates integrin-linked kinase (ILK) and the known inhibitory effect of ILK on glycogen synthase kinase 3 (GSK-3), the authors determined that in transfected cells, the regulation of AP-1 by FN is mediated through stimulation of ILK and the subsequent inhibition of GSK-3. Although ILK is known to activate protein kinase B (PKB/AKT), this apparently was not involved in the stimulation of AP-1 by FN. The authors propose that inhibition of GSK-3 might prevent phosphorylation of the DNA-binding domain of c-jun, a central component of all AP-1 protein complexes. This would then promote binding to DNA and stimulation of AP-1 activity.

Troussard, A.A., Tan, C., Yoganathan, N., and Dedhar, S. (1999) Cell-extracellular matrix interactions stimulate the AP-1 transcription factor in an integrin-linked kinase- and glycogen synthase kinase 3-dependent manner. Mol. Cell. Biol. 19: 7420-7427. [Online Journal]