title: ADAM-mediated ectodomain shedding of HB-EGF in receptor cross-talk.
abstract: All ligands of the epidermal growth factor receptor (EGFR) which has important roles in development and disease, are shed from the plasma membrane by metalloproteases. The ectodomain shedding of EGFR ligands has emerged as a critical component in the functional activation of EGFR in the interreceptor cross-talk. Identification of the sheddases for EGFR ligands using mouse embryonic cells lacking candidate sheddases (a disintegrin and metalloprotease; ADAM) has revealed that ADAM10, -12 and -17 are the sheddases of the EGFR ligands in response to various shedding stimulants such as GPCR agonists, growth factors, cytokines, osmotic stress, wounding and phorbol ester. Among the EGFR ligands, heparin-binding EGF-like growth factor (HB-EGF) is a representative ligand to understand the pathophysiological roles of the ectodomain shedding in wound healing, cardiac diseases, etc. Here we focus on the ectodomain shedding of HB-EGF by ADAMs, which is not only a key event of receptor cross-talk but also a novel intercellular signaling by the carboxy-terminal fragment (CTF signal).
authors.affiliation: Division of Biochemistry and Molecular Genetics, Department of Molecular and Cellular Biology, Ehime University School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan. shigeki@m.ehime-u.ac.jp
authors.forename: Shigeki
authors.initials: S
authors.lastname: Higashiyama
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nanba
mesh_terms: D051722:ADAM Proteins; D000072199:ADAM12 Protein; D000072198:ADAM17 Protein; D053829:Amyloid Precursor Protein Secretases; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000502:physiology*; D006332:Cardiomegaly / Q000503:physiopathology; D010450:Endopeptidases; D004815:Epidermal Growth Factor / Q000502:physiology*; D066246:ErbB Receptors / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000502:physiology*; D008666:Metalloendopeptidases / Q000502:physiology*; D020239:Receptor Cross-Talk / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014945:Wound Healing / Q000502:physiology
chemical_list: C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D004815:Epidermal Growth Factor; D006493:Heparin; D066246:ErbB Receptors; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; C509282:Bace1 protein, mouse; D051722:ADAM Proteins; D000072199:ADAM12 Protein; C000606480:ADAM12 protein, human; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein