Iwamoto R, Mekada E
Research Institute for Microbial Diseases, Osaka University, Suita, 565-0871, Osaka, Japan.
Cytokine Growth Factor Rev. 2000 Dec;11(4):335-44. doi: 10.1016/s1359-6101(00)00013-7.
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.
肝素结合表皮生长因子样生长因子（HB-EGF）属于表皮生长因子家族生长因子，以膜锚定形式（proHB-EGF）合成。proHB-EGF在细胞外结构域的蛋白水解切割产生可溶性形式的HB-EGF（sHB-EGF）。proHB-EGF不仅是sHB-EGF的前体分子，其本身也是一种生物活性分子。最近的研究表明，proHB-EGF具有与可溶性形式不同的独特特性。proHB-EGF与包括四跨膜蛋白CD9、粘附分子整合素α3β1和硫酸乙酰肝素蛋白聚糖在内的膜蛋白形成复合物。该复合物定位于细胞间接触部位，表明proHB-EGF可能通过旁分泌机制在细胞间信号传导中发挥作用。在体外模型系统中，proHB-EGF显示出生长抑制活性，而sHB-EGF具有生长刺激作用。胞外域脱落，即膜锚定形式转化为可溶性形式，受多种信号通路调控。所有这些特征表明proHB-EGF和sHB-EGF的使用方式不同。sHB-EGF和proHB-EGF在体内的功能在很大程度上尚不明确，但最近的研究表明它们参与了包括胚泡着床和伤口愈合在内的多种生理过程。
