Structure-function relationships for the EGF/TGF-alpha family of mitogens
- PMID: 7779404
- DOI: 10.3109/08977199409010997
Structure-function relationships for the EGF/TGF-alpha family of mitogens
Abstract
Epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha) are ligands for the EGF-receptor and act as mitogens for a variety of tissues. TGF-alpha, 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-alpha 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-alpha. The difficulties associated with the purification and characterisation of analogues of EGF/TGF-alpha 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-alpha 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-alpha 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.
Similar articles
-
Epidermal growth factor contains both positive and negative determinants for interaction with ErbB-2/ErbB-3 heterodimers.Biochemistry. 2002 Apr 2;41(13):4292-301. doi: 10.1021/bi012016n. Biochemistry. 2002. PMID: 11914075
-
Contribution of the transforming growth factor alpha B-loop beta-sheet to binding and activation of the epidermal growth factor receptor.J Biol Chem. 1995 Jan 27;270(4):1612-6. J Biol Chem. 1995. PMID: 7829492
-
Non-linear antigenic regions in epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) studied by EGF-TGF alpha chimaeras.Biochem J. 2000 Jul 1;349(Pt 1):267-74. doi: 10.1042/0264-6021:3490267. Biochem J. 2000. PMID: 10861238 Free PMC article.
-
The solution structures of epidermal growth factor and transforming growth factor alpha.Prog Growth Factor Res. 1989;1(1):13-22. doi: 10.1016/0955-2235(89)90038-0. Prog Growth Factor Res. 1989. PMID: 2491252 Review.
-
Transforming growth factor alpha.Cell Biol Int. 1995 May;19(5):373-88. doi: 10.1006/cbir.1995.1083. Cell Biol Int. 1995. PMID: 7640654 Review.
Cited by
-
Prostate Cancer in African American Men: The Effect of Androgens and microRNAs on Epidermal Growth Factor Signaling.Horm Cancer. 2016 Dec;7(5-6):296-304. doi: 10.1007/s12672-016-0271-4. Epub 2016 Jul 22. Horm Cancer. 2016. PMID: 27447901 Free PMC article. Review.
-
Identification of betacellulin as a major peptide growth factor in milk: purification, characterization and molecular cloning of bovine betacellulin.Biochem J. 1999 Dec 15;344 Pt 3(Pt 3):713-21. Biochem J. 1999. PMID: 10585857 Free PMC article.
-
The ErbB signaling network: receptor heterodimerization in development and cancer.EMBO J. 2000 Jul 3;19(13):3159-67. doi: 10.1093/emboj/19.13.3159. EMBO J. 2000. PMID: 10880430 Free PMC article. Review. No abstract available.
-
Piptides: New, Easily Accessible Chemotypes For Interactions With Biomolecules.Angew Chem Int Ed Engl. 2021 Mar 15;60(12):6653-6659. doi: 10.1002/anie.202015203. Epub 2021 Feb 4. Angew Chem Int Ed Engl. 2021. PMID: 33319463 Free PMC article.
-
The role of epidermal growth factor receptor in cancer metastasis and microenvironment.Biomed Res Int. 2013;2013:546318. doi: 10.1155/2013/546318. Epub 2013 Aug 7. Biomed Res Int. 2013. PMID: 23986907 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials