KGF Receptor: Transforming Potential on Fibroblasts and Epithelial Cell-Specific Expression by Alternative Splicing

Abstract

The mouse keratinocyte growth factor (KGF) receptor (KGFR) cDNA was isolated by an expression cDNA cloning strategy involving creation of a transforming autocrine loop. Characterization of the cloned 4.2 kb cDNA revealed a predicted membrane-spanning tyrosine kinase structurally related to the FGF receptor (FGFR). Structural analysis of the human KGFR cloned by the analogous procedure revealed identity with one of the fibroblast growth factor (FGF) receptors (bek/FGFR-2) except for a divergent stretch of 49 amino acids in their extracellular domains. Binding assays demonstrated that the KGFR was a high affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic FGF and acidic FGF but no detectable binding by KGF. Analysis of the bek gene revealed two alternative exons responsible for the region of divergence between the two receptors. The KGFR transcript was specific to epithelial cells, and it appeared to be differentially regulated with respect to the alternative FGFR-2 transcript.