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Biomedical subjects

E Fortney

Publications and source records attributed to E Fortney.

2 recordsLinked to original sources

Keratinocyte growth factor.

Keratinocyte growth factor (KGF) is a member of the heparin-binding fibroblast growth factor family (FGF-7) with a distinctive pattern of target-cell specificity. Studies performed in cell culture suggested that KGF was mitogenically active only on epithelial cells, albeit from a variety of tissues. In contrast, KGF was produced solely by cells of mesenchymal origin, leading to the hypothesis that it might function as a paracrine mediator of mesenchymal-epithelial communication. Biochemical analysis and molecular cloning established that the KGF receptor (KGFR) was a tyrosine kinase isoform encoded by the fgfr-2 gene. Many detailed investigations of KGF and KGFR expression in whole tissue and cell lines largely substantiated the pattern initially perceived in vitro of mesenchymal and epithelial distribution, respectively. Moreover, functional assays in organ culture and in vivo and studies of KGF regulation by sex steroid hormones reinforced the idea that KGF acts predominantly on epithelial cells to elicit a variety of responses including proliferation, migration and morphogenesis.

Animals↗

A keratinocyte growth factor receptor-derived peptide antagonist identifies part of the ligand binding site.

Keratinocyte growth factor (KGF) is a fibroblast growth factor (FGF) family member that acts specifically on cells of epithelial origin. Its receptor (KGFR) is a membrane-spanning tyrosine kinase, which also binds acidic FGF (aFGF) with equally high affinity, and basic FGF (bFGF) with much lower affinity. The KGFR is encoded by the bek/FGFR-2 gene, whose alternative transcript specifies a receptor with high affinity for aFGF and bFGF, but no detectable binding of KGF. The only structural difference between these two receptors is a 49-amino acid segment in the extracellular domain that is determined by single alternative exons. We report that a synthetic peptide (NH2-His199...Tyr223-COOH) corresponding to part of the predicted sequence of the KGFR alternative exon blocks KGF mitogenic activity and the interaction between KGF and its receptor. The peptide also blocks the interaction between KGF and a neutralizing monoclonal antibody raised against this growth factor. These results demonstrate that the peptide binds directly and specifically to KGF and argue that this region of the receptor constitutes part or all of the KGF binding site.

3T3 Cells↗