Marti U, Burwen S J, Jones A L
Cell Biology and Aging Section, Veterans Administration Medical Center, San Francisco, California 94121.
Hepatology. 1989 Jan;9(1):126-38. doi: 10.1002/hep.1840090122.
Epidermal growth factor (EGF) is a 6,000 Da polypeptide hormone produced by glands of the gastrointestinal tract, namely the salivary and Brunner's glands. It is found in a wide variety of external secretions as well as in blood and amniotic fluid. In fetal and neonatal life, EGF appears to play an important role in the development of the oral cavity, lungs, gastrointestinal tract and eyelids. Its presence in cells of the central nervous system suggests that it also plays a role in modulating the development of this system. In adult animals, the function of EGF is much less well understood. In rodents, it apparently modulates acid secretion from parietal cells in the stomach, and it undoubtedly plays an important role in wound healing, either through its localization within skin or by the licking of wounds with EGF-containing saliva. Considerable evidence now suggests that it may be one of the key factors in initiating liver regeneration after partial hepatectomy or chemical injury. The liver appears to be the principal organ which regulates the circulating level of EGF. In fact, EGF is cleared so efficiently by the liver that only the peripheral cells of the lobule (zone 1) sequester EGF, and little remains in the circulation for cells in the more distal zones (zones 2 and 3). In the liver, EGF normally binds to a plasma membrane receptor and is internalized within the liver cell, where the vast majority of EGF and its receptor are destroyed in lysosomes. A small but consistent quantity of EGF enters the bile intact. In the regenerating liver, however, the lysosomal pathway appears to be shut down, and the EGF is diverted to hepatocyte nuclei prior to the initiation of DNA synthesis. Nuclear EGF is found free as well as bound to a high-molecular-weight protein which has many characteristics identical to the plasma membrane EGF receptor. The plasma membrane receptor is a large transmembrane glycoprotein of 170,000 Da containing four domains: an extracellular EGF-binding portion, a hydrophobic membrane-spanning segment, a proximal cytoplasmic domain which binds ATP and protein substrates containing tyrosine for phosphorylation and a terminal cytoplasmic portion with 3 tyrosines which undergo autophosphorylation after EGF binding.(ABSTRACT TRUNCATED AT 400 WORDS)
表皮生长因子（EGF）是一种由胃肠道腺体，即唾液腺和布伦纳腺产生的6000道尔顿的多肽激素。它存在于多种外分泌液以及血液和羊水中。在胎儿和新生儿期，EGF似乎在口腔、肺、胃肠道和眼睑的发育中发挥重要作用。它在中枢神经系统细胞中的存在表明它在调节该系统的发育中也起作用。在成年动物中，EGF的功能了解得要少得多。在啮齿动物中，它显然调节胃壁细胞的酸分泌，并且它无疑在伤口愈合中起重要作用，要么通过其在皮肤中的定位，要么通过用含EGF的唾液舔伤口。现在有大量证据表明，它可能是部分肝切除或化学损伤后启动肝再生的关键因素之一。肝脏似乎是调节EGF循环水平的主要器官。事实上，肝脏对EGF的清除非常有效，以至于只有小叶的外周细胞（1区）能隔离EGF，而在更远端区域（2区和3区）的细胞中，循环中几乎没有剩余的EGF。在肝脏中，EGF通常与质膜受体结合并被内化到肝细胞内，在那里绝大多数EGF及其受体在溶酶体中被破坏。一小部分但数量稳定的EGF完整地进入胆汁。然而，在再生肝脏中，溶酶体途径似乎被关闭，并且在DNA合成开始之前，EGF被转移到肝细胞核。在细胞核中发现游离的EGF以及与一种高分子量蛋白质结合的EGF，这种蛋白质具有许多与质膜EGF受体相同的特征。质膜受体是一种170000道尔顿的大型跨膜糖蛋白，包含四个结构域：一个细胞外EGF结合部分、一个疏水跨膜片段、一个近端细胞质结构域，该结构域结合ATP和含酪氨酸的蛋白质底物进行磷酸化，以及一个末端细胞质部分，其中有3个酪氨酸，在EGF结合后会发生自磷酸化。（摘要截选至400字）
