Construction and characterization of a high activity mutant of human keratinocyte growth factor-2
Keratinocyte growth factor-2 (KGF-2) plays an important role in vertebrate limb development, lung branching morphogenesis, regeneration and reconstruction of the epidermis. Previous studies have used the wild type factor. Here, we have constructed a double-site mutant of human KGF-2, named STEA. STEA possesses higher receptor binding affinity and promotes better proliferation activity on rat tracheal epithelium (RTE) cells than recombinant human KGF-2. These results suggest that the simultaneous mutation of Ser115 to Thr and Glu117 to Ala improves the biological activity of KGF-2.
KeywordsCell proliferation Keratinocyte growth factor receptor Keratinocyte growth factor-2 Mutation
The authors would like to thank Professor Peitang Huang and Dr. Junjie Yue for their helpful suggestions for the design of the KGF-2 mutant.
- Anteby EY, Natanson-Yaron S, Hamani Y, Sciaki Y, Goldman-Wohl D, Greenfield C, Ariel I, Yagel S (2005) Fibroblast growth factor-10 and fibroblast growth factor receptors 1–4: expression and peptide localization in human decidua and placenta. Eur J Obstet Gynecol Reprod Biol 119:27–35PubMedCrossRefGoogle Scholar
- Beer HD, Vindevoghel L, Gait MJ, Revest JM, Duan DR, Mason I, Dickson C, Werner S (2000) Fibroblast growth factor (FGF) receptor 1-IIIb is a naturally occurring functional receptor for FGFs that is preferentially expressed in the skin and the brain. J Biol Chem 275:16091–16097PubMedCrossRefGoogle Scholar
- Sandborn WJ, Sands BE, Wolf DC, Valentine JF, Safdi M, Katz S, Isaacs KL, Wruble LD, Katz J, Present DH, Loftus EV, Graeme-Cook F, Odenheimer DJ, Hanauer SB (2003) Repifermin (keratinocyte growth factor-2) for the treatment of active ulcerative colitis: a randomized, double-blind, placebo-controlled, dose-escalation trial. Aliment Pharmacol Ther 17:1355–1364PubMedCrossRefGoogle Scholar
- Sher I, Weizman A, Lubinsky-Mink S, Lang T, Adir N, Schomburg D, Ron D (1999) Mutations uncouple human fibroblast growth factor (FGF)-7 biological activity and receptor binding and support broad specificity in the secondary receptor binding site of FGFs. J Biol Chem 274:35016–35022PubMedCrossRefGoogle Scholar