Structure-function relationships for the EGF/TGF-α family of mitogens

Leo C. Groenen, Edouard C. Nice, Antony W. Burgess

Research output: Contribution to journalReview ArticleResearchpeer-review

215 Citations (Scopus)


Epidermal growth factor (EGF) and transforming growth factor alpha (TGF-α are ligands for the EGF-receptor and act as mitogens for a variety of tissues. TGF-α in particular, has been implicated as an autocrine growth factor for several cancer cell lines. Over the last 10 years many groups have examined the structure-function relationships in EGF/TGF-α in attempts to develop antagonists or agonists. In this review the results of these studies are summarised and related to the three-dimensional structure of EGF/TGF-α The dificulties associated with the purification and characterisation of analogues of EGF/TGF-α and with the biological assays are discussed. It is clear that these difficulties have, in some cases, led to apparently contradicting results. The available binding data indicate that the receptor interaction surface for EGF/TGF-α might encompass one complete side of the molecule with a few strong binding determinants, in particular Arg41 and Leu47. The arginine at position 41 is the most critical residue and its full hydrogen-bonding capacity is needed for strong binding of EGF/TGF-α to the EGF-receptor. As this side of the molecule consists of residues from both the N- and C-terminal domain, it seems unlikely that agonists or antagonists can be developed on the basis of short peptides taken from the primary sequence. This concept is supported by the available binding and activity data.

Original languageEnglish
Pages (from-to)235-257
Number of pages23
JournalGrowth Factors
Issue number4
Publication statusPublished - 1 Jan 1994
Externally publishedYes


  • Amphiregulin
  • Betacellulin
  • Biological assays
  • Epidermal growth factor
  • HB-EGF
  • Heregulin
  • Receptor binding
  • Structure/activity relationships
  • Transforming growth factor alpha
  • Vaccinia growth factor

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