Heparin-binding EGF-like growth factor: a juxtacrine growth factor.
Heparin-binding EGF-like growth factor (HB-EGF), which belongs to the EGF-family growth factors, is synthesized as a membrane-anchored form (proHB-EGF). Proteolytic cleavage of proHB-EGF at the extracellular domain yields the soluble form of HB-EGF (sHB-EGF). ProHB-EGF is not only the precursor molecule for sHB-EGF but also a biologically active molecule itself. Recent studies indicate that proHB-EGF has unique properties distinct from the soluble form. ProHB-EGF forms a complex with membrane proteins including a tetramembrane spanning protein: CD9, an adhesion molecule integrin: alpha3beta1, and heparan sulfate proteoglycans. The complex is localized at the cell-cell contact site, suggesting that proHB-EGF may function in cell-to-cell signaling by a juxtacrine mechanism. In an in vitro model system, proHB-EGF showed growth inhibitory activity, while sHB-EGF was growth stimulatory. Ectodomain shedding, conversion of the membrane-anchored form into the soluble form, is regulated by multiple signaling pathways. All these characteristics imply that proHB-EGF and sHB-EGF are used in different ways. In vivo functions of sHB-EGF and proHB-EGF have been largely undefined, but recent studies implicate them in a variety of physiological processes including blastocyst implantation and wound healing.
Iwamoto
R
R
Research Institute for Microbial Diseases, Osaka University, Suita, 565-0871, Osaka, Japan.
Mekada
E
E
D000818:Animals; D010064:Embryo Implantation / Q000502:physiology; D004815:Epidermal Growth Factor / Q000737:chemistry / Q000502:physiology*; D005260:Female; D006493:Heparin / Q000502:physiology*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000502:physiology; D008954:Models, Biological; D011247:Pregnancy; D011498:Protein Precursors / Q000737:chemistry / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology; D015398:Signal Transduction; D014945:Wound Healing / Q000502:physiology
C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011498:Protein Precursors; D011956:Receptors, Cell Surface; D004815:Epidermal Growth Factor; D006493:Heparin