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Gene Review

Hbegf  -  heparin-binding EGF-like growth factor

Mus musculus

Synonyms: AW047313, Dtr, Dts, HB-EGF, Hegfl, ...
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Disease relevance of Hbegf


Psychiatry related information on Hbegf

  • Our findings suggest that regional and temporal differences in the availability of endogenous HB-EGF may serve to limit the response of EGL neuroblasts to opioids, and HB-EGF may be neuroprotective in opiate drug abuse [6].

High impact information on Hbegf


Chemical compound and disease context of Hbegf


Biological context of Hbegf


Anatomical context of Hbegf


Associations of Hbegf with chemical compounds

  • Together, our observations suggest that retinoid receptor heterodimers located in differentiated suprabasal cells mediate retinoid induction of HB-EGF, which in turn stimulates basal cell growth via intercellular signaling [10].
  • It was concluded that HB-EGF activation of receptor tyrosine kinases is essential for normal heart function [16].
  • Epithelial morphogenesis was inhibited by a synthetic peptide corresponding to the heparin-binding domain of HB-EGF and by anti-HB-EGF neutralizing antibody [11].
  • Unexpectedly, however, neither chlorate nor hexadimethrine treatment caused an inhibition of HB-EGF-induced mitogenic activity [12].
  • A single topical treatment of either 12-O-tetradecanoylphorbol-13-acetate (TPA) or chrysarobin or a single full-thickness wound induced the expression of HB-EGF and AR in mRNA samples isolated from whole mouse skin [1].

Enzymatic interactions of Hbegf

  • It was concluded that MMP-3 cleaves HB-EGF at a specific site in the JM domain and that this enzyme might regulate the conversion of HB-EGF from being a juxtacrine to a paracrine/autocrine growth factor [17].

Regulatory relationships of Hbegf


Other interactions of Hbegf


Analytical, diagnostic and therapeutic context of Hbegf


  1. Altered expression of epidermal growth factor receptor ligands in tumor promoter-treated mouse epidermis and in primary mouse skin tumors induced by an initiation-promotion protocol. Kiguchi, K., Beltrán, L., Rupp, T., DiGiovanni, J. Mol. Carcinog. (1998) [Pubmed]
  2. Soluble form of heparin-binding EGF-like growth factor contributes to retinoic acid-induced epidermal hyperplasia. Kimura, R., Iwamoto, R., Mekada, E. Cell Struct. Funct. (2005) [Pubmed]
  3. Heparin binding EGF is necessary for vasospastic response to endothelin. Chansel, D., Ciroldi, M., Vandermeersch, S., Jackson, L.F., Gomez, A.M., Henrion, D., Lee, D.C., Coffman, T.M., Richard, S., Dussaule, J.C., Tharaux, P.L. FASEB J. (2006) [Pubmed]
  4. Loss of HB-EGF in smooth muscle or endothelial cell lineages causes heart malformation. Nanba, D., Kinugasa, Y., Morimoto, C., Koizumi, M., Yamamura, H., Takahashi, K., Takakura, N., Mekada, E., Hashimoto, K., Higashiyama, S. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  5. Overexpression of heparin-binding EGF-like growth factor in mouse pancreas results in fibrosis and epithelial metaplasia. Means, A.L., Ray, K.C., Singh, A.B., Washington, M.K., Whitehead, R.H., Harris, R.C., Wright, C.V., Coffey, R.J., Leach, S.D. Gastroenterology (2003) [Pubmed]
  6. Opposing actions of the EGF family and opioids: heparin binding-epidermal growth factor (HB-EGF) protects mouse cerebellar neuroblasts against the antiproliferative effect of morphine. Opanashuk, L.A., Hauser, K.F. Brain Res. (1998) [Pubmed]
  7. Cardiac hypertrophy is inhibited by antagonism of ADAM12 processing of HB-EGF: metalloproteinase inhibitors as a new therapy. Asakura, M., Kitakaze, M., Takashima, S., Liao, Y., Ishikura, F., Yoshinaka, T., Ohmoto, H., Node, K., Yoshino, K., Ishiguro, H., Asanuma, H., Sanada, S., Matsumura, Y., Takeda, H., Beppu, S., Tada, M., Hori, M., Higashiyama, S. Nat. Med. (2002) [Pubmed]
  8. Rapid induction of heparin-binding epidermal growth factor/diphtheria toxin receptor expression by Raf and Ras oncogenes. McCarthy, S.A., Samuels, M.L., Pritchard, C.A., Abraham, J.A., McMahon, M. Genes Dev. (1995) [Pubmed]
  9. Tonic-clonic seizures induce division of neuronal progenitor cells with concomitant changes in expression of neurotrophic factors in the brain of pilocarpine-treated mice. Hagihara, H., Hara, M., Tsunekawa, K., Nakagawa, Y., Sawada, M., Nakano, K. Brain Res. Mol. Brain Res. (2005) [Pubmed]
  10. Identification of heparin-binding EGF-like growth factor as a target in intercellular regulation of epidermal basal cell growth by suprabasal retinoic acid receptors. Xiao, J.H., Feng, X., Di, W., Peng, Z.H., Li, L.A., Chambon, P., Voorhees, J.J. EMBO J. (1999) [Pubmed]
  11. Involvement of heparin-binding EGF-like growth factor and its processing by metalloproteinases in early epithelial morphogenesis of the submandibular gland. Umeda, Y., Miyazaki, Y., Shiinoki, H., Higashiyama, S., Nakanishi, Y., Hieda, Y. Dev. Biol. (2001) [Pubmed]
  12. Differential effects of a heparin antagonist (hexadimethrine) or chlorate on amphiregulin, basic fibroblast growth factor, and heparin-binding EGF-like growth factor activity. Cook, P.W., Ashton, N.M., Karkaria, C.E., Siess, D.C., Shipley, G.D. J. Cell. Physiol. (1995) [Pubmed]
  13. Defective valvulogenesis in HB-EGF and TACE-null mice is associated with aberrant BMP signaling. Jackson, L.F., Qiu, T.H., Sunnarborg, S.W., Chang, A., Zhang, C., Patterson, C., Lee, D.C. EMBO J. (2003) [Pubmed]
  14. HaCaT keratinocyte migration is dependent on epidermal growth factor receptor signaling and glycogen synthase kinase-3alpha. Koivisto, L., Jiang, G., Häkkinen, L., Chan, B., Larjava, H. Exp. Cell Res. (2006) [Pubmed]
  15. Multiple trophic actions of heparin-binding epidermal growth factor (HB-EGF) in the central nervous system. Kornblum, H.I., Zurcher, S.D., Werb, Z., Derynck, R., Seroogy, K.B. Eur. J. Neurosci. (1999) [Pubmed]
  16. Heparin-binding EGF-like growth factor and ErbB signaling is essential for heart function. Iwamoto, R., Yamazaki, S., Asakura, M., Takashima, S., Hasuwa, H., Miyado, K., Adachi, S., Kitakaze, M., Hashimoto, K., Raab, G., Nanba, D., Higashiyama, S., Hori, M., Klagsbrun, M., Mekada, E. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  17. Matrix metalloproteinase-3 releases active heparin-binding EGF-like growth factor by cleavage at a specific juxtamembrane site. Suzuki, M., Raab, G., Moses, M.A., Fernandez, C.A., Klagsbrun, M. J. Biol. Chem. (1997) [Pubmed]
  18. Heparin-binding epidermal growth factor-like growth factor stimulates cell proliferation in cerebral cortical cultures through phosphatidylinositol 3'-kinase and mitogen-activated protein kinase. Jin, K., Mao, X.O., Del Rio Guerra, G., Jin, L., Greenberg, D.A. J. Neurosci. Res. (2005) [Pubmed]
  19. Rapid phosphorylation of Ets-2 accompanies mitogen-activated protein kinase activation and the induction of heparin-binding epidermal growth factor gene expression by oncogenic Raf-1. McCarthy, S.A., Chen, D., Yang, B.S., Garcia Ramirez, J.J., Cherwinski, H., Chen, X.R., Klagsbrun, M., Hauser, C.A., Ostrowski, M.C., McMahon, M. Mol. Cell. Biol. (1997) [Pubmed]
  20. Induction of heparin-binding EGF-like growth factor expression during myogenesis. Activation of the gene by MyoD and localization of the transmembrane form of the protein on the myotube surface. Chen, X., Raab, G., Deutsch, U., Zhang, J., Ezzell, R.M., Klagsbrun, M. J. Biol. Chem. (1995) [Pubmed]
  21. Heparin-binding epidermal growth factor-like growth factor: hypoxia-inducible expression in vitro and stimulation of neurogenesis in vitro and in vivo. Jin, K., Mao, X.O., Sun, Y., Xie, L., Jin, L., Nishi, E., Klagsbrun, M., Greenberg, D.A. J. Neurosci. (2002) [Pubmed]
  22. Heparin-binding EGF-like growth factor gene is induced in the mouse uterus temporally by the blastocyst solely at the site of its apposition: a possible ligand for interaction with blastocyst EGF-receptor in implantation. Das, S.K., Wang, X.N., Paria, B.C., Damm, D., Abraham, J.A., Klagsbrun, M., Andrews, G.K., Dey, S.K. Development (1994) [Pubmed]
  23. Prolactin regulation by heparin-binding growth factors expressed in mouse pituitary cell lines. Hnasko, R., Ben-Jonathan, N. Endocrine (2003) [Pubmed]
  24. Gastrin enhances the angiogenic potential of endothelial cells via modulation of heparin-binding epidermal-like growth factor. Clarke, P.A., Dickson, J.H., Harris, J.C., Grabowska, A., Watson, S.A. Cancer Res. (2006) [Pubmed]
  25. Heparin-binding EGF-like growth factor: characterization of rat and mouse cDNA clones, protein domain conservation across species, and transcript expression in tissues. Abraham, J.A., Damm, D., Bajardi, A., Miller, J., Klagsbrun, M., Ezekowitz, R.A. Biochem. Biophys. Res. Commun. (1993) [Pubmed]
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