RRC ID |
41863
|
Author |
Shin SY, Yokoyama T, Takenouchi T, Munekata E.
|
Title |
The chemical synthesis and binding affinity to the EGF receptor of the EGF-like domain of heparin-binding EGF-like growth factor (HB-EGF).
|
Journal |
J Pept Sci
|
Abstract |
Heparin-binding EGF-like growth factor (HB-EGF), which belongs to the EGF-family of growth factors, was isolated from the conditioned medium of macrophage-like cells. To investigate the effect of N- and C-terminal residues of the EGF-like domain of HB-EGF in the binding affinity to the EGF receptor on A431 cell. We synthesized HB-EGF(44-86) corresponding to the EGF-like domain of HB-EGF and its N- or C-terminal truncated peptides. Thermolytic digestion demonstrated three disulfide bond pairings of the EGF-like domain in HB-EGF is consistent with that of human-EGF and human-TGF-alpha. HB-EGF(44-86) showed high binding affinity to EGF-receptor, like human-EGF. The truncation of the C-terminal Leu86 residue from HB-EGF(44-86), HB-EGF(45-86) or HB-EGF(46-86) caused a drastic reduction in the binding affinity to the EGF receptor. These results suggest that the EGF-like domain of HB-EGF plays an important role in the binding to the EGF receptor, and its C-terminal Leu86 residue is necessary for binding with the EGF-receptor. In addition, the deletion of the two N-terminal residues (Asp44-Pro45) from HB-EGF(44-86) caused a 10-fold decrease in relative binding affinity to the EGF receptor. This indicates that the two N-terminal residues of the EGF-like domain of HB-EGF are necessary for its optimal binding affinity to the EGF receptor.
|
Volume |
9(4)
|
Pages |
244-50
|
Published |
2003-4-1
|
DOI |
10.1002/psc.450
|
PMID |
12725245
|
MeSH |
Amino Acid Sequence
Binding Sites
Cell Line, Tumor
Epidermal Growth Factor / chemical synthesis
Epidermal Growth Factor / chemistry*
Epidermal Growth Factor / metabolism*
ErbB Receptors / metabolism*
Heparin-binding EGF-like Growth Factor
Humans
Intercellular Signaling Peptides and Proteins
Peptide Fragments / chemical synthesis
Protein Binding
Protein Structure, Tertiary
Transforming Growth Factor alpha / chemistry
|
IF |
1.877
|
Times Cited |
4
|
WOS Category
|
CHEMISTRY, ANALYTICAL
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
Resource |
Human and Animal Cells |
A431(RCB0202) |