Higashiyama S, Abraham JA, Miller J, Fiddes JC, Klagsbrun M. A heparin-binding growth factor secreted by macrophage-like cells that is related to EGF. Science. 1991;251(4996):936–9.

Article  ADS  CAS  PubMed  Google Scholar 

Thompson SA, Higashiyama S, Wood K, Pollitt NS, Damm D, McEnroe G, Garrick B, Ashton N, Lau K, Hancock N, et al. Characterization of sequences within heparin-binding EGF-like growth factor that mediate interaction with heparin. J Biol Chem. 1994;269(4):2541–9.

Article  CAS  PubMed  Google Scholar 

Earp HS, Dawson TL, Li X, Yu H. Heterodimerization and functional interaction between EGF receptor family members: a new signaling paradigm with implications for breast cancer research. Breast Cancer Res Treat. 1995;35(1):115–32.

Article  CAS  PubMed  Google Scholar 

Plowman GD, Whitney GS, Neubauer MG, Green JM, McDonald VL, Todaro GJ, Shoyab M. Molecular cloning and expression of an additional epidermal growth factor receptor-related gene. Proc Natl Acad Sci U S A. 1990;87(13):4905–9.

Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

Plowman GD, Culouscou JM, Whitney GS, Green JM, Carlton GW, Foy L, Neubauer MG, Shoyab M. Ligand-specific activation of HER4/p180erbB4, a fourth member of the epidermal growth factor receptor family. Proc Natl Acad Sci U S A. 1993;90(5):1746–50.

Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

Higashiyama S, Lau K, Besner GE, Abraham JA, Klagsbrun M. Structure of heparin-binding EGF-like growth factor. Multiple forms, primary structure, and glycosylation of the mature protein. J Biol Chem. 1992;267(9):6205–12.

Article  CAS  PubMed  Google Scholar 

Elenius K, Paul S, Allison G, Sun J, Klagsbrun M. Activation of HER4 by heparin-binding EGF-like growth factor stimulates chemotaxis but not proliferation. EMBO J. 1997;16(6):1268–78.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Elenius K, Corfas G, Paul S, Choi CJ, Rio C, Plowman GD, Klagsbrun M. A novel juxtamembrane domain isoform of HER4/ErbB4. Isoform-specific tissue distribution and differential processing in response to phorbol ester. J Biol Chem. 1997;272(42):26761–8.

Article  CAS  PubMed  Google Scholar 

Carraway KL 3rd, Cantley LC. A neu acquaintance for erbB3 and erbB4: a role for receptor heterodimerization in growth signaling. Cell. 1994;78(1):5–8.

Article  CAS  PubMed  Google Scholar 

Higashiyama S, Abraham JA, Klagsbrun M. Heparin-binding EGF-like growth factor stimulation of smooth muscle cell migration: dependence on interactions with cell surface heparan sulfate. J Cell Biol. 1993;122(4):933–40.

Article  CAS  PubMed  Google Scholar 

Shishido Y, Sharma KD, Higashiyama S, Klagsbrun M, Mekada E. 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 factor. J Biol Chem. 1995;270(49):29578–85.

Article  CAS  PubMed  Google Scholar 

Aviezer D, Yayon A. Heparin-dependent binding and autophosphorylation of epidermal growth factor (EGF) receptor by heparin-binding EGF-like growth factor but not by EGF. Proc Natl Acad Sci U S A. 1994;91(25):12173–7.

Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

Raab G, Klagsbrun M. Heparin-binding EGF-like growth factor. Biochim Biophys Acta. 1997;1333(3):F179–99.

CAS  PubMed  Google Scholar 

Massague J, Pandiella A. Membrane-anchored growth factors. Annu Rev Biochem. 1993;62:515–41.

Article  CAS  PubMed  Google Scholar 

Goishi K, Higashiyama S, Klagsbrun M, Nakano N, Umata T, Ishikawa M, Mekada E, Taniguchi N. Phorbol ester induces the rapid processing of cell surface heparin-binding EGF-like growth factor: conversion from juxtacrine to paracrine growth factor activity. Mol Biol Cell. 1995;6(8):967–80.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Izumi Y, Hirata M, Hasuwa H, Iwamoto R, Umata T, Miyado K, Tamai Y, Kurisaki T, Sehara-Fujisawa A, Ohno S, Mekada E. A metalloprotease-disintegrin, MDC9/meltrin-gamma/ADAM9 and PKCdelta are involved in TPA-induced ectodomain shedding of membrane-anchored heparin-binding EGF-like growth factor. EMBO J. 1998;17(24):7260–72.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Raab G, Kover K, Paria BC, Dey SK, Ezzell RM, Klagsbrun M. Mouse preimplantation blastocysts adhere to cells expressing the transmembrane form of heparin-binding EGF-like growth factor. Development. 1996;122(2):637–45.

Article  CAS  PubMed  Google Scholar 

Nakamura K, Iwamoto R, Mekada E. Membrane-anchored heparin-binding EGF-like growth factor (HB-EGF) and diphtheria toxin receptor-associated protein (DRAP27)/CD9 form a complex with integrin alpha 3 beta 1 at cell-cell contact sites. J Cell Biol. 1995;129(6):1691–705.

Article  CAS  PubMed  Google Scholar 

Mekada E, Okada Y, Uchida T. Identification of diphtheria toxin receptor and a nonproteinous diphtheria toxin-binding molecule in Vero cell membrane. J Cell Biol. 1988;107(2):511–9.

Article  CAS  PubMed  Google Scholar 

Naglich JG, Metherall JE, Russell DW, Eidels L. Expression cloning of a diphtheria toxin receptor: identity with a heparin-binding EGF-like growth factor precursor. Cell. 1992;69(6):1051–61.

Article  CAS  PubMed  Google Scholar 

Higashiyama S, Iwamoto R, Goishi K, Raab G, Taniguchi N, Klagsbrun M, Mekada E. The membrane protein CD9/DRAP 27 potentiates the juxtacrine growth factor activity of the membrane-anchored heparin-binding EGF-like growth factor. J Cell Biol. 1995;128(5):929–38.

Article  CAS  PubMed  Google Scholar 

Iwamoto R, Senoh H, Okada Y, Uchida T, Mekada E. An antibody that inhibits the binding of diphtheria toxin to cells revealed the association of a 27-kDa membrane protein with the diphtheria toxin receptor. J Biol Chem. 1991;266(30):20463–9.

Article  CAS  PubMed  Google Scholar 

Iwamoto R, Higashiyama S, Mitamura T, Taniguchi N, Klagsbrun M, Mekada E. Heparin-binding EGF-like growth factor, which acts as the diphtheria toxin receptor, forms a complex with membrane protein DRAP27/CD9, which up-regulates functional receptors and diphtheria toxin sensitivity. EMBO J. 1994;13(10):2322–30.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lanzrein M, Garred O, Olsnes S, Sandvig K. Diphtheria toxin endocytosis and membrane translocation are dependent on the intact membrane-anchored receptor (HB-EGF precursor): studies on the cell-associated receptor cleaved by a metalloprotease in phorbol-ester-treated cells. Biochem J. 1995;310(Pt 1):285–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Diaz B, Yuen A, Iizuka S, Higashiyama S, Courtneidge SA. Notch increases the shedding of HB-EGF by ADAM12 to potentiate invadopodia formation in hypoxia. J Cell Biol. 2013;201(2):279–92.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li P, Deng Q, Liu J, Yan J, Wei Z, Zhang Z, Liu H, Li B. Roles for HB-EGF in mesenchymal stromal cell proliferation and differentiation during skeletal growth. J Bone Miner Res. 2019;34(2):295–309.

Article  CAS  PubMed  Google Scholar 

Puschmann TB, Zanden C, Lebkuechner I, Philippot C, de Pablo Y, Liu J, Pekny M. HB-EGF affects astrocyte morphology, proliferation, differentiation, and the expression of intermediate filament proteins. J Neurochem. 2014;128(6):878–89.

Article  CAS  PubMed  Google Scholar 

Kim YS, Yuan J, Dewar A, Borg JP, Threadgill DW, Sun X, Dey SK. An unanticipated discourse of HB-EGF with VANGL2 signaling during embryo implantation. Proc Natl Acad Sci U S A. 2023;120(20):e2302937120.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liu J, Gao F, Liu YF, Dou HT, Yan JQ, Fan ZM, Yang ZM. HB-EGF regulates Prss56 expression during mouse decidualization via EGFR/ERK/EGR2 signaling pathway. J Endocrinol. 2017;234(3):247–54.

Article  CAS  PubMed  Google Scholar 

Wang X, Wang H, Matsumoto H, Roy SK, Das SK, Paria BC. Dual source and target of heparin-binding EGF-like growth factor during the onset of implantation in the hamster. Development. 2002;129(17):4125–34.

Article  CAS  PubMed  Google Scholar 

Kim YJ, Lee GS, Hyun SH, Ka HH, Choi KC, Lee CK, Jeung EB. Uterine expression of epidermal growth factor family during the course of pregnancy in pigs. Reprod Domest Anim. 2009;44(5):797–804.

Article  CAS  PubMed  Google Scholar 

Kim GY, Besner GE, Steffen CL, McCarthy DW, Downing MT, Luquette MH, Abad MS, Brigstock DR. Purification of heparin-binding epidermal growth factor-like growth factor from pig uterine luminal flushings, and its production by endometrial tissues. Biol Reprod. 1995;52(3):561–71.

Article  CAS  PubMed  Google Scholar 

Kliem A, Tetens F, Klonisch T, Grealy M, Fischer B. Epidermal growth factor receptor and ligands in elongating bovine blastocysts. Mol Reprod Dev. 1998;51(4):402–12.