Roles of Keratinocyte Growth Factor in Epithelial Growth and Regeneration

Abstract

Keratinocyte growth factor (KGF) is a cytokine that was first identified in 1989 as a mesenchymally derived paracrine mediator of epithelial cell growth (1–3). Upon sequencing, approximately 35% to 40% homology was found with other members of the fibroblast growth factor (FGF) family; hence, KGF is designated as FGF7. In contrast to many other members of the FGF family, cells responsive to KGF appear to be confined to epithelial lineages (4). The KGF receptor (KGFR) is an alternatively spliced tyrosine kinase product of the FGF receptor 2 gene (FGFR2, bek) (5, 6). KGF and acidic FGF (FGF1) bind with high affinity to KGFR, while basic FGF (FGF2) binds with lower affinity (7, 8). The basis for a more KGF selective binding to the KGFR is found in a 49 amino acid stretch beginning in the C-terminal half of the third immunoglobulin loop in FGFR2 (9). A synthetic peptide from this region can block KGF interaction with the KGFR, demonstrating the specificity for KGF conferred by the alternative splicing event (10). Further work suggests elements of the second 1 g loop are also important for high-affinity binding to KGF (11). In contrast to acidic and basic FGF, KGF has a signal sequence and is secreted from mesenchymal cells in a conventional manner.