Heparin-dependent binding and autophosphorylation of epidermal growth factor (EGF) receptor by heparin-binding EGF-like growth factor but not by EGF.
Heparin-binding EGF-like growth factor (HB-EGF) is a recently identified member of the EGF family of growth factors and a potent mitogen for smooth muscle cells and fibroblasts. Chinese hamster ovary (CHO) cells genetically engineered to express the human EGF receptor bind with high affinity both EGF and HB-EGF. CHO mutant cells lacking heparan sulfate proteoglycans ( HSPG) bind EGF equally well to wild-type cells and EGF binding is not affected by exogenous heparin. However, HSPG-deficient EGF receptor- expressing cells do not bind significant levels of HB-EGF unless heparin is present in the binding medium. Moreover, binding of radiolabeled EGF to HSPG-deficient EGF receptor- expressing cells is efficiently displaced by nonlabeled HB-EGF only in the presence of heparin. Signal transduction by the EGF receptor tyrosine kinase as evidenced by receptor autophosphorylation is induced by HB-EGF only in the presence of heparin, in contrast to EGF-induced receptor autophosphorylation, which is independent of heparin. These results directly demonstrate that HB-EGF but not EGF requires heparin or cell surface HSPG for binding and activation of the EGF receptor and that HB-EGF receptor interactions can be tightly regulated by the available local concentration of heparin-like molecules.[1]References
- Heparin-dependent binding and autophosphorylation of epidermal growth factor (EGF) receptor by heparin-binding EGF-like growth factor but not by EGF. Aviezer, D., Yayon, A. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg