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

该项目的长期目标是利用小鼠模型了解罗恩（一种受体酪氨酸激酶）在植入和早期发育过程中的生物学功能。 初步研究将集中在野生型动物胚胎植入过程中罗恩及其配体肝细胞生长因子样蛋白的时空特征。接下来，将确定与植入期间罗恩功能丧失相关的异常表型，并通过表征罗恩-/-胚胎周围的滋养层细胞的分化和侵袭能力来探索缺失该受体的效果。最后，将在已建立的滋养层细胞系（从野生型到高度侵袭性）中通过失活或过表达来操纵罗恩受体，以阐明植入期间配体诱导的罗恩激活所涉及的分子机制。这些实验将不仅导致更好地了解罗恩的表达和功能在哺乳动物植入和早期发展，但也可能牵连的潜在意义，罗恩功能异常的侵入性条件，如子宫腺瘤和异位妊娠。

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.