Significance of the entire C-terminus in biological activities mediated by the RON receptor tyrosine kinase and its oncogenic variant RON160
<p>Abstract</p> <p>The RON receptor tyrosine kinase regulates epithelial cell homeostasis and tumorigenesis by transducing multiple signals through its functional domains. The present study was to determine the significance of the entire C-terminus in RON or its variant RON160-medi...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2008-10-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Online Access: | http://www.jeccr.com/content/27/1/55 |
| _version_ | 1811249400714887168 |
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| author | Yao Hang-Ping Lu Yi Wang Ming-Hai |
| author_facet | Yao Hang-Ping Lu Yi Wang Ming-Hai |
| author_sort | Yao Hang-Ping |
| collection | DOAJ |
| description | <p>Abstract</p> <p>The RON receptor tyrosine kinase regulates epithelial cell homeostasis and tumorigenesis by transducing multiple signals through its functional domains. The present study was to determine the significance of the entire C-terminus in RON or its variant RON160-mediated activities related to cell motility and tumorigenesis. Analysis of protein phosphorylation revealed that elimination of the entire C-terminus significantly impairs the ligand-dependent or independent RON or RON160 phosphorylation and dimerization. Phosphorylation of downstream signaling proteins such as Erk1/2, AKT, and p38 MAP kinase was also diminished in cells expressing the C-terminus-free RON or RON160. These dysfunctional activities were accompanied with the inability of truncated RON or RON160 to mediate cytoplasmic β-catenin accumulation. Functional analysis further demonstrated that truncation of the C-terminus significantly impairs RON or RON160-mediated cell proliferation, morphological changes, and cellular migration. Significantly, oncogenic RON160-mediated tumor growth in athymic nude mice was lost after the deletion of the C-terminus. Thus, the C-terminus is a critical component of the RON receptor. The entire C-terminus is required for RON or RON160-mediated intracellular signaling events leading to various cellular activities.</p> |
| first_indexed | 2024-04-12T15:45:53Z |
| format | Article |
| id | doaj.art-ddb9200bfb2e446f8de3280c79fdf91c |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-04-12T15:45:53Z |
| publishDate | 2008-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-ddb9200bfb2e446f8de3280c79fdf91c2022-12-22T03:26:40ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662008-10-012715510.1186/1756-9966-27-55Significance of the entire C-terminus in biological activities mediated by the RON receptor tyrosine kinase and its oncogenic variant RON160Yao Hang-PingLu YiWang Ming-Hai<p>Abstract</p> <p>The RON receptor tyrosine kinase regulates epithelial cell homeostasis and tumorigenesis by transducing multiple signals through its functional domains. The present study was to determine the significance of the entire C-terminus in RON or its variant RON160-mediated activities related to cell motility and tumorigenesis. Analysis of protein phosphorylation revealed that elimination of the entire C-terminus significantly impairs the ligand-dependent or independent RON or RON160 phosphorylation and dimerization. Phosphorylation of downstream signaling proteins such as Erk1/2, AKT, and p38 MAP kinase was also diminished in cells expressing the C-terminus-free RON or RON160. These dysfunctional activities were accompanied with the inability of truncated RON or RON160 to mediate cytoplasmic β-catenin accumulation. Functional analysis further demonstrated that truncation of the C-terminus significantly impairs RON or RON160-mediated cell proliferation, morphological changes, and cellular migration. Significantly, oncogenic RON160-mediated tumor growth in athymic nude mice was lost after the deletion of the C-terminus. Thus, the C-terminus is a critical component of the RON receptor. The entire C-terminus is required for RON or RON160-mediated intracellular signaling events leading to various cellular activities.</p>http://www.jeccr.com/content/27/1/55 |
| spellingShingle | Yao Hang-Ping Lu Yi Wang Ming-Hai Significance of the entire C-terminus in biological activities mediated by the RON receptor tyrosine kinase and its oncogenic variant RON160 Journal of Experimental & Clinical Cancer Research |
| title | Significance of the entire C-terminus in biological activities mediated by the RON receptor tyrosine kinase and its oncogenic variant RON160 |
| title_full | Significance of the entire C-terminus in biological activities mediated by the RON receptor tyrosine kinase and its oncogenic variant RON160 |
| title_fullStr | Significance of the entire C-terminus in biological activities mediated by the RON receptor tyrosine kinase and its oncogenic variant RON160 |
| title_full_unstemmed | Significance of the entire C-terminus in biological activities mediated by the RON receptor tyrosine kinase and its oncogenic variant RON160 |
| title_short | Significance of the entire C-terminus in biological activities mediated by the RON receptor tyrosine kinase and its oncogenic variant RON160 |
| title_sort | significance of the entire c terminus in biological activities mediated by the ron receptor tyrosine kinase and its oncogenic variant ron160 |
| url | http://www.jeccr.com/content/27/1/55 |
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