Cross-talk between insulin receptor and integrin alpha5 beta1 signaling pathways
Program in Molecular Medicine and Department of Biochemistry and Molecular Biology
1-Phosphatidylinositol 3-Kinase; Androstadienes; Animals; CHO Cells; Cell Adhesion; Cricetinae; Fibronectins; Insulin; Integrins; Oligopeptides; Phosphoproteins; Phosphorylation; Receptor, Insulin; Receptors, Fibronectin; Signal Transduction; Tyrosine
Life Sciences | Medicine and Health Sciences
The ligation and clustering of cell surface alphabeta heterodimeric integrins enhances cell adhesion and initiates signaling pathways that regulate such processes as cell spreading, migration, differentiation, proliferation and apoptosis. Here we show that insulin treatment of Chinese hamster ovary cells expressing insulin receptors (CHO-T) markedly promotes cell adhesion onto a fibronectin matrix, but not onto bovine serum albumin or poly-lysine. Incubation of cells with a GRGDSP peptide that specifically binds integrins (but not the nonspecific GRADSP peptide) abolishes this insulin effect, as does the potent phosphoinositide 3-kinase (PI 3-kinase) inhibitor wortmannin. Moreover, a specific blocking monoclonal anti-alpha5beta1 integrin antibody, PB-1, blocks insulin-stimulated cell adhesion onto fibronectin. Conversely, activating alpha5beta1 integrins on CHO-T cells by adherence onto fibronectin markedly potentiates the action of insulin to enhance insulin receptor and insulin receptor substrate (IRS)-1 tyrosine phosphorylation. Activation of alpha5beta1 integrin also markedly potentiates the recruitment of p85-associated PI 3-kinase activity to IRS-1 in response to submaximal levels of insulin in CHO-T cells. These data indicate that insulin potently activates integrin alpha5beta1 mediated CHO-T cell adhesion, while integrin alpha5beta1 signaling in turn enhances insulin receptor kinase activity and formation of complexes containing IRS-1 and PI 3-kinase. These findings raise the hypothesis that insulin receptor and alpha5beta1 integrin signaling act synergistically to enhance cell adhesion.
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Citation: J Biol Chem. 1998 Sep 4;273(36):22899-903.
The Journal of biological chemistry
Guilherme, Adilson L.; Torres, Kevin; and Czech, Michael P., "Cross-talk between insulin receptor and integrin alpha5 beta1 signaling pathways" (1998). Open Access Articles. 777.