Platelet-derived growth factor (PDGF) is a disulfide-linked dimer consisting of two related polypeptide chains, designated PDGF A and PDGF B. The gene encoding the human PDGF B chain is the normal counterpart of the v-sis oncogene. Understanding PDGF signal transduction and transcriptional activation is a first step toward inhibiting PDGF related malignant processes. We demonstrated that PDGF treatment of fibroblasts induced tyrosine phosphorylation of Jak1, Stat6, Stat5a, and Stat5b. Interleukin-4 (IL-4) enhanced PDGF-induced proliferation as well as tyrosine phosphorylation of Jak1 and Stat6, but not Stat5. These results provide evidence that Stat6 and Jak1 are common elements in PDGF and IL-4 signaling pathways and suggest that IL-4 could potentiate certain PDGF-induced biologic responses. Hepatocyte growth factor (HGF) is a multifunctional paracrine mediator of epithelial cell growth. An in vivo oncogenic role for HGF has not been demonstrated. Transgenic mice inappropriately overexpressing HGF developed a broad array of histologically distinct tumors of mesenchymal and epithelial origin. Sarcomas and hepatocellular carcinomas were identified that overexpressed both transgenic HGF and endogenous Met. Transgenic mouse liver weight doubled in comparison to that of wild-type mice. The mechanistic basis of hepatocyte proliferation was revealed as the chronic activation of the c-met proto-oncogene product. After partial hepatectomy, transgenic livers regenerated at a three-fold faster rate than control livers. A transgenic hepatocyte cell line was established exhibiting chronic Met, PI3-kinase, Shc, Src, FAK, and paxillin tyrosine phosphorylation. Thus, HGF stimulated hepatic proliferation, regeneration, and oncogenesis when overexpressed in vivo, suggesting a prominent role for HGF in regulating normal liver growth, repair, and development. These HGF transgenic mice should provide excellent animal models for future studies of HGF-induced malignant processes.