Hepatocyte growth factor/scatter factor (HGF/SF) structure-function analysis demonstrated that the amino-terminal domain is solely responsible for the heparin-binding properties of the full-length molecule. Site-directed mutagenesis in this domain resulted both in weaker heparin-binding and reduced mitogenic activity. Sex steroid regulation of HGF/SF and its receptor, as well as keratinocyte growth factor (KGF) and its receptor, was analyzed in mouse uterus. In a collaborative study, endocrine precursor cells from human pancreas were stimulated by HGF/SF to proliferate ex vivo and matured to form functional islets following transplantation into nude mice. In another collaborative project, HGF/SF transgenic mice were generated and exhibited several abnormal phenotypes. Work is in progress both to study these animals and establish cell lines from their tissues. In vivo experiments with KGF established that exogenous administration of the factor had a dramatic protective effect in a rat model of hyperoxia-induced lung injury. Expression studies involving a recently cloned protein structurally related to frizzled, a tissue polarity gene in Drosophila, indicated that it is synthesized by many cells, including several human carcinoma cell lines. A cDNA fragment of the mouse homolog of the frizzled-related protein (provisionally termed FRP) was isolated to facilitate analysis of its expression during development and in the adult.
