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  • Original Article
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Oncogenic Met receptor induces ectopic structures in Xenopus embryos

Abstract

When aberrantly expressed or activated, the Met receptor tyrosine kinase is involved in tumor invasiveness and metastasis. In this study, we have used the Xenopus embryonic system to define the role of various Met proximal-binding partners and downstream signaling pathways in regulating an induced morphogenetic event. We show that expression of an oncogenic derivative of the Met receptor (Tpr-Met) induces ectopic morphogenetic structures during Xenopus embryogenesis. Using variant forms of Tpr-Met that are engineered to recruit a specific signaling molecule of choice, we demonstrate that the sole recruitment of either the Grb2 or the Shc adaptor protein is sufficient to induce ectopic structures and anterior reduction, while the recruitment of PI-3Kinase (PI-3K) is necessary but not sufficient for this effect. In contrast, the recruitment of PLCĪ³ can initiate the induction, but fails to maintain or elongate supernumerary structures. Finally, evidence indicates that the Ras/Raf/MAPK pathway is necessary, but not sufficient to induce these structures. This study also emphasizes the importance of examining signaling molecules in the regulatory context that is provided by receptor/effector interactions when assessing a role in cell growth and differentiation.

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Acknowledgements

We thank Morag Park for helpful discussions, Deborah Morrison for DnKSR, Malcolm Whitman for RasN17, and Tom Sargent, Jonathan Slack, John Gurdon, Sally Moody, Christof Niehrs, I Dawid for in situ constructs. AI was supported by a Japan Society for the Promotion of Science Research Fellowship. This research was supported by the Intramural Research Program of the NIH, NCI.

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Correspondence to I O Daar.

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Ishimura, A., Lee, HS., Bong, YS. et al. Oncogenic Met receptor induces ectopic structures in Xenopus embryos. Oncogene 25, 4286ā€“4299 (2006). https://doi.org/10.1038/sj.onc.1209463

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