Schepper J M, Hughes E F, Postel-Vinay M C, Hughes J P
J Biol Chem. 1984 Nov 10;259(21):12945-8.
Several studies have shown that proteolytic cleavage can enhance the biological activity of the growth hormone (GH) molecule. It seemed possible, therefore, that proteolytic modification of GH might be a normal function of GH-target tissues. Plasmalemma-enriched fractions isolated from rabbit liver were found to contain a proteinase(s) which cleaves the large disulfide loop of human and rat GH. The proteolytic activity was specific to plasmalemma-enriched fractions in that much lower activities were observed in microsomal-enriched fractions prepared from the same livers. The plasmalemmal proteinase(s) may be a trypsin-like enzyme because proteolytic activity was decreased by two serine proteinase inhibitors. Inhibition by unlabeled human GH of 125I-GH binding to receptors did not prevent cleavage of the tracer; therefore, hormone-receptor interaction was not required for cleavage of the GH molecule. In binding studies, cleaved GH associated more readily than did intact hormone with rabbit liver receptors. These studies suggest that plasmalemma-enriched fractions prepared from rabbit liver contain a proteinase which cleaves the GH molecule in a highly specific manner. Moreover, it is unlikely that inactivation of GH is the function of this limited proteolysis because cleaved hormone is bound preferentially by at least a subset of receptors in rabbit liver.
多项研究表明，蛋白水解切割可增强生长激素（GH）分子的生物活性。因此，GH的蛋白水解修饰可能是GH靶组织的正常功能。从兔肝脏分离的富含质膜的组分被发现含有一种蛋白酶，该蛋白酶可切割人和大鼠GH的大的二硫键环。这种蛋白水解活性对富含质膜的组分具有特异性，因为在从相同肝脏制备的富含微粒体的组分中观察到的活性要低得多。质膜蛋白酶可能是一种类胰蛋白酶，因为两种丝氨酸蛋白酶抑制剂可降低蛋白水解活性。未标记的人GH对125I-GH与受体结合的抑制作用并不能阻止示踪剂的切割；因此，GH分子的切割不需要激素-受体相互作用。在结合研究中，与完整激素相比，切割后的GH与兔肝脏受体的结合更易于发生。这些研究表明，从兔肝脏制备的富含质膜的组分含有一种蛋白酶，该蛋白酶以高度特异性的方式切割GH分子。此外，GH失活不太可能是这种有限蛋白水解的功能，因为切割后的激素优先被兔肝脏中至少一部分受体结合。
