Mitogen-inducible gene 6 is an endogenous inhibitor of HGF/Met-induced cell migration and neurite growth
| Autor: | Ingvar Ferby, Alun M. Davies, Fabienne Lamballe, Guido Pante, Tomoko Iwata, Jane Thompson, Rüdiger Klein, Flavio Maina, Francis A. Barr |
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| Přispěvatelé: | Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
Small interfering RNA
Neurite Protein Conformation medicine.medical_treatment CDC42 [SDV.BC]Life Sciences [q-bio]/Cellular Biology Biology Article Cell Line Mice 03 medical and health sciences 0302 clinical medicine Cell Movement Neurites medicine Animals RNA Messenger cdc42 GTP-Binding Protein Research Articles Adaptor Proteins Signal Transducing 030304 developmental biology 0303 health sciences Hepatocyte Growth Factor Growth factor Intracellular Signaling Peptides and Proteins Cell migration Cell Biology Molecular biology rac GTP-Binding Proteins Cell biology Rac GTP-Binding Proteins Gene Expression Regulation 030220 oncology & carcinogenesis Hepatocyte growth factor Signal transduction Signal Transduction medicine.drug |
| Zdroj: | Journal of Cell Biology Journal of Cell Biology, Rockefeller University Press, 2005, 171, pp.337-348 Journal of Cell Biology, 2005, 171, pp.337-348 The Journal of Cell Biology |
| ISSN: | 0021-9525 1540-8140 |
| Popis: | Hepatocyte growth factor (HGF)/Met signaling controls cell migration, growth and differentiation in several embryonic organs and is implicated in human cancer. The physiologic mechanisms that attenuate Met signaling are not well understood. Here we report a mechanism by which mitogen-inducible gene 6 (Mig6; also called Gene 33 and receptor-associated late transducer) negatively regulates HGF/Met-induced cell migration. The effect is observed by Mig6 overexpression and is reversed by Mig6 small interfering RNA knock-down experiments; this indicates that endogenous Mig6 is part of a mechanism that inhibits Met signaling. Mig6 functions in cells of hepatic origin and in neurons, which suggests a role for Mig6 in different cell lineages. Mechanistically, Mig6 requires an intact Cdc42/Rac interactive binding site to exert its inhibitory action, which suggests that Mig6 acts, at least in part, distally from Met, possibly by inhibiting Rho-like GTPases. Because Mig6 also is induced by HGF stimulation, our results suggest that Mig6 is part of a negative feedback loop that attenuates Met functions in different contexts and cell types. |
| Databáze: | OpenAIRE |
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