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Alpha 5 beta 1 integrin activates an NF-kappa B-dependent program of gene expression important for angiogenesis and
Sharon Klein1, Antonin R de Fougerolles, Pamela Blaikie
1Cellular Biochemistry and Biophysics Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Abstract:
GeneCalling, a genome-wide method of mRNA profiling, reveals that endothelial cells adhering to fibronectin through the alpha 5 beta 1 integrin, but not to laminin through the alpha 2 beta 1 integrin, undergo a complex program of gene expression. Several of the genes identified are regulated by the NF-kappa B transcription factor, and many are implicated in the regulation of inflammation and angiogenesis. Adhesion of endothelial cells to fibronectin activates NF-kappa B through a signaling pathway requiring Ras, phosphatidylinositol 3-kinase, and Rho family proteins, whereas adhesion to laminin has a limited effect. Retroviral transfer of the superrepressor of NF-kappa B, I kappa B-2A, blocks basic fibroblast growth factor-induced angiogenesis in vivo. These results suggest that engagement of the alpha 5 beta 1 integrin promotes an NF-kappa B-dependent program of gene expression that coordinately regulates angiogenesis and inflammation.