title: 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 PLCgamma 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.
authors.affiliation: Laboratory of Protein Dynamics & Signaling, National Cancer Institute-Frederick, MD 21702, USA.
authors.forename: A
authors.initials: A
authors.lastname: Ishimura
authors.forename: H-S
authors.initials: HS
authors.lastname: Lee
authors.forename: Y-S
authors.initials: YS
authors.lastname: Bong
authors.forename: C
authors.initials: C
authors.lastname: Saucier
authors.forename: K
authors.initials: K
authors.lastname: Mood
authors.forename: E K
authors.initials: EK
authors.lastname: Park
authors.forename: I O
authors.initials: IO
authors.lastname: Daar
mesh_terms: D000818:Animals; D004625:Embryo, Nonmammalian / Q000378:metabolism*; D004627:Embryonic Induction / Q000502:physiology*; D005260:Female; D009154:Mutation; D010766:Phosphorylation; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000502:physiology*; D014981:Xenopus
chemical_list: D019859:Proto-Oncogene Proteins c-met