Journal article
beta 3 Integrin-EGF receptor cross-talk activates p190RhoGAP in mouse mammary gland epithelial cells
Molecular biology of the cell, Vol.22(22), pp.4288-4301
11/15/2011
DOI: 10.1091/mbc.E10-08-0700
PMCID: PMC3216655
PMID: 21937717
Abstract
Active RhoA localizes to plasma membrane, where it stimulates formation of focal adhesions and stress fibers. RhoA activity is inhibited by p190RhoGAP following integrin-mediated cell attachment to allow sampling of new adhesive environments. p190RhoGAP is itself activated by Src-dependent tyrosine phosphorylation, which facilitates complex formation with p120RasGAP. This complex then translocates to the cell surface, where p190RhoGAP down-regulates RhoA. Here we demonstrate that the epidermal growth factor receptor (EGFR) cooperates with beta 3 integrin to regulate p190RhoGAP activity in mouse mammary gland epithelial cells. Adhesion to fibronectin stimulates tyrosine phosphorylation of the EGFR in the absence of receptor ligands. Use of a dominant inhibitory EGFR mutant demonstrates that fibronectin-activated EGFR recruits p120RasGAP to the cell periphery. Expression of an inactive beta 3 integrin subunit abolishes p190RhoGAP tyrosine phosphorylation, demonstrating a mechanistic link between beta 3 integrin-activated Src and EGFR regulation of the RhoA inhibitor. The beta 3 integrin/EGFR pathway also has a positive role in formation of filopodia. Together our data suggest that EGFR constitutes an important intrinsic migratory cue since fibronectin is a key component of the microenvironment in normal mammary gland development and breast cancer. Our data also suggest that EGFR expressed at high levels has a role in eliciting cell shape changes associated with epithelial-to-mesenchymal transition.
Details
- Title: Subtitle
- beta 3 Integrin-EGF receptor cross-talk activates p190RhoGAP in mouse mammary gland epithelial cells
- Creators
- Nikolas Balanis - Case Western Reserve UniversityMasaaki Yoshigi - University of UtahMichael K. Wendt - Case Western Reserve UniversityWilliam P. Schiemann - Case Western Reserve UniversityCathleen R. Carlin - Case Western Reserve University
- Resource Type
- Journal article
- Publication Details
- Molecular biology of the cell, Vol.22(22), pp.4288-4301
- DOI
- 10.1091/mbc.E10-08-0700
- PMID
- 21937717
- PMCID
- PMC3216655
- NLM abbreviation
- Mol Biol Cell
- ISSN
- 1059-1524
- eISSN
- 1939-4586
- Publisher
- Amer Soc Cell Biology
- Number of pages
- 14
- Grant note
- GM081498; CA129359 / Public Health Service; United States Department of Health & Human Services; United States Public Health Service R01GM081498 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) T32HL007653 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) P30CA043703 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) P30 CA043703 / Case Comprehensive Cancer Center HL007653 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA PF-09-120-01 / American Cancer Society
- Language
- English
- Date published
- 11/15/2011
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984459630302771
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