Schantl Julia A, Roza Marcel, Van Kerkhof Peter, Strous Ger J
Department of Cell Biology, University Medical Center Utrecht, The Netherlands.
Biochem J. 2004 Jan 15;377(Pt 2):379-84. doi: 10.1042/BJ20031321.
Proteolysis of the GHR (growth hormone receptor) occurs at the cell surface and results in the release of its extracellular domain, the GHBP (growth hormone-binding protein). TACE (tumour necrosis factor-alpha-converting enzyme) has been identified as a putative protease responsible for GHR cleavage. However, GHR-TACE interaction has not been observed until now. Here, we identified TACE in Chinese hamster cells and confirmed processing and cell-surface expression. Interaction between GHR and TACE was only observed after growth hormone binding. As the growth hormone-GHR(2) complex is a poor substrate for TACE, we conclude that the GHR-TACE interaction precedes proteolysis, and is transient. Furthermore, we demonstrate that TACE is present in endosomes, where it partly co-localizes with endocytosed growth hormone ligand.
生长激素受体（GHR）的蛋白水解发生在细胞表面，导致其细胞外结构域即生长激素结合蛋白（GHBP）的释放。肿瘤坏死因子-α转换酶（TACE）已被确定为一种可能负责GHR裂解的蛋白酶。然而，迄今为止尚未观察到GHR与TACE的相互作用。在此，我们在中国仓鼠细胞中鉴定出TACE，并证实了其加工过程和细胞表面表达。仅在生长激素结合后才观察到GHR与TACE之间的相互作用。由于生长激素-GHR(2)复合物是TACE的不良底物，我们得出结论，GHR与TACE的相互作用先于蛋白水解，并且是短暂的。此外，我们证明TACE存在于内体中，它在内体中与内吞的生长激素配体部分共定位。
