Engineering epidermal growth factor for enhanced mitogenic potency

Nat Biotechnol. 1996 Dec;14(13):1696-9. doi: 10.1038/nbt1296-1696.


Successful use of growth factors in therapeutic and bioprocessing applications requires overcoming two attenuation mechanisms: growth factor depletion and receptor down-regulation. Current ameliorative strategies use physiologically inappropriate high growth-factor concentrations, along with periodic media refeeding in vitro and reinjection or controlled-release devices in vivo. We demonstrate a new approach derived from understanding how these attenuation mechanisms arise from ligand/receptor trafficking processes. Specifically, a recombinant epidermal growth factor (EGF) mutant with reduced receptor binding affinity is a more potent mitogenic stimulus for fibroblasts than natural EGF or transforming growth factor alpha because of its altered trafficking properties.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 3T3 Cells
  • Animals
  • Cell Division / drug effects
  • Down-Regulation / drug effects
  • Epidermal Growth Factor / biosynthesis*
  • Epidermal Growth Factor / genetics
  • Epidermal Growth Factor / pharmacology
  • ErbB Receptors / metabolism
  • Fibroblasts / drug effects
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics*
  • Genetic Engineering
  • Mice
  • Mitogens / biosynthesis*
  • Mitogens / genetics
  • Mitogens / pharmacology
  • Mutation / genetics
  • Recombinant Proteins / genetics
  • Signal Transduction / drug effects
  • Transforming Growth Factor alpha / genetics
  • Transforming Growth Factor alpha / pharmacology


  • Mitogens
  • Recombinant Proteins
  • Transforming Growth Factor alpha
  • Epidermal Growth Factor
  • ErbB Receptors