THE BIOLOGY OF RON/STK, A RECEPTOR TRYOSINE KINASE.

Children'S Hospital Med Ctr (Cincinnati), Cincinnati OH

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Abstract

The long term goal of this project is to understand the biological function(s) of Ron, a receptor tyrosine kinase during implantation and early development using a murine model. Initial studies will focus on the temporal and spatial characterization of Ron and its ligand, hepatocyte growth factor-like protein, during embryonic implantation in wild type animals. Next, the abnormal phenotype correlated with the loss of Ron function during implantation will be determined and the effect of deleting this receptor will be explored by characterizing the differentiation and invasion ability of trophoblast cells surrounding Ron -/- embryos. Finally, manipulation of the Ron receptor via inactivation or overexpression in established trophoblast cell lines (ranging from wild type to highly invasive) will be performed to elucidate the molecular mechanisms involved in ligand induced Ron activation during implantation. These experiments will not only lead to a better understanding of Ron expression and function during mammalian implantation and early development but may also implicate the potential significance of Ron function anomalies during invasive conditions such as uterine adenomas and ectopic pregnancies.