title: The growth hormone receptor interacts with its sheddase, the tumour necrosis factor-alpha-converting enzyme (TACE).
abstract: 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.
mesh_terms: D051722:ADAM Proteins; D000072198:ADAM17 Protein; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D011992:Endosomes / Q000737:chemistry / Q000201:enzymology; D013006:Growth Hormone / Q000032:analysis; D008168:Lung / Q000166:cytology; D008666:Metalloendopeptidases / Q000032:analysis / Q000378:metabolism*; D011233:Precipitin Tests; D011986:Receptors, Somatotropin / Q000032:analysis / Q000378:metabolism*
chemical_list: D011986:Receptors, Somatotropin; D013006:Growth Hormone; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein