Lane M D, Slieker L J, Olson T S, Martensen T M
J Recept Res. 1987;7(1-4):321-54. doi: 10.3109/10799898709054992.
The epidermal growth factor receptor (EGFR) and insulin receptor undergo slow post-translational modification by which they acquire hormone binding and tyrosine kinase (EGFR) function. The half-time for acquisition of EGF or insulin binding activity is 30-40 min and of tyrosine kinase activity (EGFR), is 10-15 min. Tunicamycin, an inhibitor of N-linked oligosaccharide addition, blocks acquisition of both EGF and insulin binding activity. With EGFR, activation precedes acquisition of resistance to endoglucosaminidase H (t1/2 approximately equal to 75 min), a medial Golgi event. Treatment of active high mannose receptor with endo H generates fully active aglyco-receptor; thus, core oligosaccharide addition is a prerequisite for activation, but not for EGF binding per se. EGFR is activated in and translocated from the endoplasmic reticulum (ER) slowly (t1/2 approximately equal to 75 min). Since translocation rate equals the rate for acquisition of endo H resistance, transit from the ER is rate limiting for EGFR maturation. Tunicamycin inhibits exit from the ER parallel to its effect on acquisition of binding activity. Insulin proreceptor, a 210 kDa high-mannose glycopolypeptide, acquires insulin binding function (t1/2 approximately equal to 45 min) then is proteolytically cleaved (t1/2 approximately equal to 3 hr) into subunits of the mature alpha 2 beta 2 receptor. Modification giving rise to insulin binding activity is due to a conformational change in the binding domain, since human autoimmune antibody recognizes only the active species, while rabbit polyclonal antibody recognizes all forms. Newly-translated EGF proreceptor lacks a functional tyrosine domain capable of autophosphorylation; 30-40 min after translation, while still in the ER, tyrosine kinase activity is acquired. Since the kinase domain is cytoplasmic, the receptor may become phosphorylated on tyrosine before reaching the plasma membrane.
表皮生长因子受体（EGFR）和胰岛素受体经历缓慢的翻译后修饰，借此获得激素结合和酪氨酸激酶（EGFR）功能。获得表皮生长因子（EGF）或胰岛素结合活性的半衰期为30 - 40分钟，而获得酪氨酸激酶活性（EGFR）的半衰期为10 - 15分钟。衣霉素是一种N - 连接寡糖添加的抑制剂，可阻断EGF和胰岛素结合活性的获得。对于EGFR，激活先于对内切葡糖胺酶H的抗性获得（t1/2约等于75分钟），这是高尔基体中间的一个事件。用内切葡糖胺酶H处理活性高甘露糖受体可产生完全活性的无糖基受体；因此，核心寡糖的添加是激活的先决条件，但不是EGF结合本身的先决条件。EGFR在从内质网（ER）激活并转位的过程缓慢（t1/2约等于75分钟）。由于转位速率等于获得内切葡糖胺酶H抗性的速率，从内质网的转运是EGFR成熟的限速步骤。衣霉素抑制从内质网的输出，与其对结合活性获得的影响平行。胰岛素原受体是一种210 kDa的高甘露糖糖多肽，获得胰岛素结合功能（t1/2约等于45分钟），然后被蛋白水解切割（t1/2约等于3小时）成成熟α2β2受体的亚基。产生胰岛素结合活性的修饰是由于结合结构域的构象变化，因为人类自身免疫抗体仅识别活性形式，而兔多克隆抗体识别所有形式。新翻译的EGF原受体缺乏能够自磷酸化的功能性酪氨酸结构域；翻译后30 - 40分钟，仍在内质网时，获得酪氨酸激酶活性。由于激酶结构域位于细胞质中，受体在到达质膜之前可能在酪氨酸上发生磷酸化。
