STRUCTURE-FUNCTION-RELATIONSHIPS FOR THE EGF/TGF-ALPHA FAMILY OF MITOGENS

Groenen, LC; Nice, EC; Burgess, AW

Author(s): Groenen, LC; Nice, EC; Burgess, AW;
Details: Publication Year 1994,Volume 11,Issue #4,Page 235-257
Journal Title: GROWTH FACTORS
Publication Type: Journal Article
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.
Publisher: HARWOOD ACAD PUBL GMBH
Keywords: EPIDERMAL GROWTH-FACTOR; SITE-DIRECTED MUTAGENESIS; NUCLEAR-MAGNETIC-RESONANCE; PROTEIN-TYROSINE KINASE; TWO-DIMENSIONAL H-1-NMR; HIGH-RESOLUTION H-1-NMR; ACID-SEQUENCE HOMOLOGY; COAGULATION FACTOR-IX; SHOPE FIBROMA VIRUS; EGF-LIKE MODULE
Publisher's Version: https://doi.org/10.3109/08977199409010997
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 1994-01-01 12:00:00