Skip to main content

Advertisement

SpringerLink
Log in

Construction and characterization of a high activity mutant of human keratinocyte growth factor-2

  • Original Research Paper
  • Published:
Biotechnology Letters Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • 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 119:27–35

    Article  PubMed  CAS  Google Scholar 

  • Bagai S, Rubio E, Cheng JF, Sweet R, Thomas R, Fuchs E, Grady R, Mitchell M, Bassuk JA (1999) Fibroblast growth factor-10 is a mitogen for urothelial cells. J Biol Chem 277:23828–23837

    Article  Google 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 275:16091–16097

    Article  PubMed  CAS  Google Scholar 

  • Brian KY, Makoto I, Anna VE, Alexander NP, Ifat S, Dina R, Stuart AA, Moosa M (2003) Structural basis by which alternative splicing confers specificity in fibroblast growth factor receptors. Proc Nat Acad Sci USA 100:2266–2271

    Article  Google Scholar 

  • Igarashi M, Finch PW, Aaronson SA (1998) Characterization of recombinant human fibroblast growth factor (FGF)-10 reveals functional similarities with keratinocyte growth factor (FGF-7). J Biol Chem 273:13230–13235

    Article  PubMed  CAS  Google Scholar 

  • Komi-Kuramochi A, Kawano M, Oda Y, Asada M, Suzuki M, Oki J, Imamura T (2005) Expression of fibroblast growth factors and their receptors during full-thickness skin wound healing in young and aged mice. J Endocrinol 186:273–289

    Article  PubMed  CAS  Google Scholar 

  • Min H, Danilenko DM, Scully SA, Bolon B, Ring BD, Tarpley JE, DeRose M, Simonet WS (1998) FGF-10 is required for both limb and lung development and exhibits striking functional similarity to Drosophila branchless. Genes Dev 12:3156–3161

    Article  PubMed  CAS  Google Scholar 

  • Miura T (2008) Modeling lung branching morphogenesis. Curr Top Dev Biol 81:291–310

    Article  PubMed  Google Scholar 

  • Ohuchi H, Hori Y, Yamasaki M, Harada H, Sekine K, Kato S, Itoh N (2000) FGF10 acts as a major ligand for FGF receptor 2 IIIb in mouse multi-organ development. Biochem Biophys Res Commun 277:643–649

    Article  PubMed  CAS  Google Scholar 

  • Okunieff P, Li M, Liu W, Sun J, Fenton B, Zhang L, Ding I (2001) Keratinocyte growth factors radioprotect bowel and bone marrow but not KHT sarcoma. Am J Clin Oncol 24:491–495

    Article  PubMed  CAS  Google 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 17:1355–1364

    Article  PubMed  CAS  Google 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 274:35016–35022

    Article  PubMed  CAS  Google Scholar 

  • Sher I, Yeh BK, Mohammadi M, Adir N, Ron D (2003) Structure-based mutational analyses in FGF7 identify new residues involved in specific interaction with FGFR2IIIb. FEBS Lett 552:150–154

    Article  PubMed  CAS  Google Scholar 

  • Smith PD, Polo M, Soler PM, McClintock JS, Maggi SP, Kim YJ, Ko F, Robson CM (2000) Efficacy of growth factors in the accelerated closure of interstices in explanted meshed human skin grafts. J Burn Care Rehabil 21(1 Pt 1):5–9

    Article  PubMed  CAS  Google Scholar 

  • Yeh BK, Igarashi M, Eliseenkova AV, Plotnikov AN, Sher I, Ron D, Aaronson SA, Mohammadi M (2003) Structural basis by which alternative splicing confers specificity in fibroblast growth factor receptors. Proc Nat Acad Sci USA 100:2266–2271

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

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.

Author information

Authors and Affiliations

  1. Laboratory of Molecular Genetics, Beijing Institute of Basic Medical Sciences, 100850, Beijing, China

    Jinfeng Wang, Xin Cai, Minji Zou, Tao Xu, Shen Liu, Yuanyuan Wang, Jiaxi Wang & Donggang Xu

Authors
  1. Jinfeng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xin Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Minji Zou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tao Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shen Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yuanyuan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jiaxi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Donggang Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Donggang Xu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, J., Cai, X., Zou, M. et al. Construction and characterization of a high activity mutant of human keratinocyte growth factor-2. Biotechnol Lett 31, 797–802 (2009). https://doi.org/10.1007/s10529-009-9948-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10529-009-9948-x

Keywords

Search

Navigation