1. ¹Laboratory of Protein Dynamics & Signaling, National Cancer Institute-Frederick, Frederick, MD, USA
2. ²Molecular Oncology Group, McGill University Health Center, Montreal, Quebec, Canada

Correspondence: Dr IO Daar, Laboratory of Protein Dynamics & Signaling, National Cancer Institute-Frederick, Building 560, Room 22-3, NCI-Frederick, Frederick, MD 21702, USA. E-mail: daar@ncifcrf.gov

³Current address: The 21st Century Center of Excellence (COE) Program, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.

⁴Current address: Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, Daegu 700-412, South Korea.

Received 31 October 2005; Revised 17 January 2006; Accepted 17 January 2006; Published online 6 March 2006.

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 PLC 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.