Integrin-induced EGFR activation and control of the cell cycle in epithelial cells

Miranti, C. K., Bill, H. M., Modres, S. L., Rao, V. R., Knudsen, B., Muthuswamy, S. K., Brugge, J. S. (March 2003) Integrin-induced EGFR activation and control of the cell cycle in epithelial cells. Faseb Journal, 17 (5). A974-A974. ISSN 0892-6638

Abstract

Objective: Engagement of integrin receptors induces activation of tyrosine kinase receptors, however the importance of this crosstalk in regulating cell function has not been extensively explored. Methods: Epithelial cells, Cos7, CV1 and primary prostate cells, were placed in suspension or plated on fibronectin and activation of the EGF receptor (EGFR), downstream signaling and cell cycle progression were evaluated. Results: Adhesion of cells to fibronectin induces tyrosine phosphorylation of a subset of tyrosine residues on EGFR in a ligand-independent manner. Fibronectin induced activation of EGFR is required for integrin-mediated activation of the Ras/Erk and PI-3K/Akt signaling pathways. Adhesion to fibronectin induces cyclin D1 synthesis, Rb phosphorylation and cdk4 activation in a manner dependent on EGFR, Ras/Erk and PI-3Ksignaling. However, adhesion is not sufficient to reduce p27 levels and cells fail to enter into S phase. Conclusion: Integrin-mediated attachment of epithelial cells to fibronectin stimulates the phosphorylation of select sites on EGFR, leads to the activation of specific EGFR targets, some of which are required for mid-G1 cell cycle progression. Despite the ability of integrins to mediate mid-G1 cell cycle events, they are not sufficient for entry into S phase due to a block in cyclin A synthesis.

Item Type: Paper
Additional Information: Meeting Abstract
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > EGFR
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cells

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > integrin
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
CSHL Authors:
Communities: CSHL labs > Muthuswamy lab
Depositing User: Matt Covey
Date: March 2003
Date Deposited: 08 Jul 2013 20:29
Last Modified: 08 Jul 2013 20:29
URI: http://repository.cshl.edu/id/eprint/27841

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