Metalloproteinase-mediated shedding of heparin-binding EGF-like growth factor and its pathophysiological roles.
Heparin-binding EGF-like growth factor (HB-EGF) exists as a membrane-anchored form (proHB-EGF) and as its soluble cleaved product (sHB-EGF). The conversion (ectodomain shedding) of proHB-EGF to sHB-EGF is tightly regulated by specific metalloproteinases. Ectodomain shedding plays a central role in GPCR-mediated EGFR transactivation. Antagonizing metalloproteinases can inhibit EGFR transactivation and might be of therapeutic value, for example in cardiac hypertrophy, skin remodeling and tumor growth.
Higashiyama
Shigeki
S
Division of Biochemistry and Molecular Genetics, Department of Molecular and Cellular Biology, Ehime University School of Medicine Shigenobu, Onsen-gun, Ehime, 791-0295, Japan. shigeki@m.ehime-u.ac.jp
D000818:Animals; D002318:Cardiovascular Diseases / Q000473:pathology / Q000503:physiopathology*; D004815:Epidermal Growth Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D008115:Liver Regeneration; D008666:Metalloendopeptidases / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology
D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D004815:Epidermal Growth Factor; D008666:Metalloendopeptidases