Mitogenic Activity of Keratinocyte Growth Factor Amino-Terminal Truncation Mutants: Deletion of Amino Acid Residues 1-15 through 1-27

• Published in: In vitro cellular & developmental biology. Animal Vol. 33; no. 8; pp. 606 - 607
• Main Authors: Rebecca E. Nybo, Erin N. Everton, Morris, Charles F.
• Format: Journal Article
• Language: English
• Published: Germany Society for In Vitro Biology 01.09.1997
• Subjects: Amino Acid Sequence; Amino acids; Animals; Cell Division - drug effects; Cell growth; Fibroblast Growth Factor 10; Fibroblast Growth Factor 7; Fibroblast growth factor receptors; Fibroblast Growth Factors; Gene Deletion; Growth Substances - chemistry; Growth Substances - genetics; Growth Substances - pharmacology; Keratinocytes; Keratinocytes - cytology; Mice; Molecular Sequence Data; Mutagenesis; Oligonucleotides; Peptide Fragments - pharmacology; Proteins; Receptors; Scientific Reports; Structure-Activity Relationship; Truncation
• ISSN: 1071-2690; 1543-706X
• DOI: 10.1007/s11626-997-0109-z

Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor (FGF) family with potent proliferative effects on epithelial cells (5). Although KGF shares considerable homology to acidic and basic fibroblast growth factors, it does not induce a mitogenic response in fibroblasts and is capable of high affinity binding only to its own receptor, the keratinocyte growth factor receptor. The amino acid sequence of KGF differs from other FGF family members in its extended amino terminus; however, the relationship of this extension to the biological activity or specificity of KGF is not completely understood. Purified recombinant KGF products with amino terminal proteolytic digestion of the first 18-19, or 23 amino acid residues have been shown to possess mitogenic activity (4 and A. Hsu, manuscript in preparation). Ron et al. have shown the effects of amino-terminal deletions to amino acid residues #4, #9, and #28 (internal methionine residues) on KGF structure and function. KGF mutants with truncation to amino acid residues #4 or #9 retained full mitogenic activity. A KGF truncation mutant lacking the first 27 residues showed decreased mitogenic activity, although it was able to bind KGF receptor with high affinity. We have further explored the importance of N-terminal amino acid residues #15 to #27 of KGF to mitogenic activity. A series of amino-terminal truncation mutants of KGF were made in which 15 to 27 amino acid residues were sequentially removed from the amino terminus of the mature KGF gene.