Studies have focused on defining the pattern of gene expression, structure- function relationships and receptor interactions of the epithelial cell-specific mitogen, keratinocyte growth factor (KGF), a member of the fibroblast growth factor (FGF) family. Biochemical analysis, as well as molecular cloning and recombinant expression have defined the properties of a KGF receptor and established its relationship to receptors for other members of the FGF family. Another fibroblast-derived mitogen (formerly termed epithelial cell growth factor II) has been purified, molecularly cloned and recombinantly expressed. This factor has a broad spectrum of target cells. including endothelial cells and melanocytes as well as cells of epithelial origin. It is homologous to a recently characterized mitogen, hepatocyte growth factor (HGF) and also is structurally related to plasminogen. Alternative splicing of the RNA transcribed from the growth factor gene results in the synthesis of different-sized proteins which appear to have distinct biological properties. Addition of this broad-spectrum mitogen to responsive cells results in rapid stimulation of tyrosine phosphorylation, suggesting that the growth factor receptor may have tyrosine kinase activity. Analysis of the receptor and associated signal transduction pathway(s) is underway.
