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Cross talk between c-Met and epidermal growth factor receptor during retinal pigment epithelial wound healing.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Xu, Kankan Yu, Fu-Shin X. |
| Copyright Year | 2007 |
| Abstract | PURPOSE The authors sought to determine how hepatocyte growth factor (HGF) receptor c-Met and epidermal growth factor receptor (EGFR) cross talk in response to injury in human ARPE-19 cells. METHODS A scratch wound was made on a cell monolayer of ARPE-19 cells using a sequence-comb or a pipet tip, and it was allowed to heal in the presence or absence of HGF and heparin-binding EGF-like growth factor (HB-EGF). The activation of EGFR was analyzed by immunoprecipitation with EGFR antibody, followed by Western blotting with phosphotyrosine-specific antibody. Phosphorylation of extracellular signal-regulated kinase (ERK) and AKT (a major substrate of phosphatidylinositol 3'-kinase (PI3K) was assessed by Western blotting. The release of c-Met ectodomain into the culture media was determined by Western blotting using an antibody against the extracellular region. Cell migration was assessed by Boyden chamber migration assay. RESULTS ARPE-19 cells underwent spontaneous wound healing in basal medium, and exogenously added HB-EGF and HGF significantly enhanced wound closure. Basal and growth factor-enhanced wound closures were attenuated but not slowed by hydroxyurea, a cell proliferation inhibitor. RPE cells expressed all four erbBs, and wounding induced EGFR transactivation and downstream ERK and PI3K phosphorylation in ARPE-19 cells. HGF also induced EGFR tyrosine phosphorylation. The EGFR kinase inhibitor AG1478 blocked wound- and HGF-stimulated EGFR transactivation and attenuated spontaneous and growth factor-induced wound closure. Wounding and EGFR ligands induced the release of c-Met into the culture media. Moreover, pretreatment of cells with HB-EGF impaired ARPE-19 migration toward HGF in a matrix metalloproteinase inhibitor-sensitive manner. CONCLUSIONS EGFR modulates HGF/c-Met activity by inducing c-Met ectodomain shedding, and HGF/c-Met transactivates EGFR, leading to an enhanced activation of downstream signaling pathways. Cross talk between EGFR and c-Met may play a key role in regulating RPE cell migration, proliferation, and wound healing. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://citeseerx.ist.psu.edu/viewdoc/download;jsessionid=477DFB59D57268CCCAA54EBCC2962123?doi=10.1.1.328.1579&rep=rep1&type=pdf |
| Alternate Webpage(s) | http://www.iovs.org/content/48/5/2242.full.pdf |
| PubMed reference number | 17460286v1 |
| Volume Number | 48 |
| Issue Number | 5 |
| Journal | Investigative ophthalmology & visual science |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | 1-Phosphatidylinositol 3-Kinase Cell Migration Assays Cell Proliferation Closure Culture Media Encephalomyelitis, Western Equine Epidermal Growth Factor Receptor Growth Factor Receptors Hepatocyte Growth Factor Ligands MET protein, human Matrix Metalloproteinase Inhibitors Matrix Metalloproteinases Metalloproteases Migration, Cell Phosphotyrosine Proto-Oncogene Proteins c-akt Retina Retinal Pigments Trans-Activation, Genetic Tyrosine Phosphorylation Western Blotting Wound Healing Wound Infection eIF-2 Kinase extracellular heparin hydroxyurea metalloendopeptidase inhibitor activity tyrphostin AG 1478 |
| Content Type | Text |
| Resource Type | Article |
