N-arginine dibasic convertase is a specific receptor for heparin-binding EGF-like growth factor that mediates cell migration
Open Access
- 2 July 2001
- journal article
- research article
- Published by Springer Nature in The EMBO Journal
- Vol. 20 (13) , 3342-3350
- https://doi.org/10.1093/emboj/20.13.3342
Abstract
Heparin‐binding epidermal growth factor‐like growth factor (HB‐EGF), a mitogen and chemotactic factor, binds to two receptor tyrosine kinases, erbB1 and erbB4. Now we demonstrate that HB‐EGF also binds to a novel 140 kDa receptor on MDA‐MB 453 cells. Purification of this receptor showed it to be identical to N‐arginine dibasic convertase (NRDc), a metalloendopeptidase of the M16 family. Binding to cell surface NRDc and NRDc in solution was highly specific for HB‐EGF among EGF family members. When overexpressed in cells, NRDc enhanced their migration in response to HB‐EGF but not to EGF. Conversely, inhibition of endogenous NRDc expression in cells by antisense morpholino oligonucleotides inhibited HB‐EGF‐induced cell migration. Anti‐erbB1 neutralizing antibodies completely abrogated the ability of NRDc to enhance HB‐EGF‐dependent migration, demonstrating that this NRDc activity was dependent on erbB1 signaling. Although NRDc is a metalloproteinase, enzymatic activity was not required for HB‐EGF binding or enhancement of cell migration; neither did NRDc cleave HB‐EGF. Together, these results suggest that NRDc is a novel specific receptor for HB‐EGF that modulates HB‐EGF‐induced cell migration via erbB1.Keywords
This publication has 47 references indexed in Scilit:
- NEW EMBO MEMBERS' REVIEW: The ErbB signaling network: receptor heterodimerization in development and cancerThe EMBO Journal, 2000
- Characterization of a naturally occurring ErbB4 isoform that does not bind or activate phosphatidyl inositol 3-kinaseOncogene, 1999
- A Novel Juxtamembrane Domain Isoform of HER4/ErbB4Journal of Biological Chemistry, 1997
- Heparin-like Molecules on the Cell Surface Potentiate Binding of Diphtheria Toxin to the Diphtheria Toxin Receptor/Membrane-anchored Heparin-binding Epidermal Growth Factor-like Growth FactorJournal of Biological Chemistry, 1995
- Localization of heparin-binding EGF-like growth factor in the smooth muscle cells and macrophages of human atherosclerotic plaques.Journal of Clinical Investigation, 1995
- N-arginine dibasic convertase (NRD convertase): a newcomer to the family of processing endopeptidases. An overviewBiochimie, 1994
- Biosynthesis and Processing by Phorbol Ester of the Cell Surface-Associated Precursor Form of Heparin-Binding EGF-like Growth FactorBiochemical and Biophysical Research Communications, 1994
- Heparin-Binding EGF-like Growth Factor: Characterization of Rat and Mouse cDNA Clones, Protein Domain Conservation across Species, and Transcript Expression in TissuesBiochemical and Biophysical Research Communications, 1993
- Expression cloning of a diphtheria toxin receptor: Identity with a heparin-binding EGF-like growth factor precursorCell, 1992
- An insulin epidermal growth factor-binding protein from Drosophila has insulin-degrading activity.The Journal of cell biology, 1989