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. 2004 Jan 15;377(Pt 2):379–384. doi: 10.1042/BJ20031321

The growth hormone receptor interacts with its sheddase, the tumour necrosis factor-alpha-converting enzyme (TACE).

Julia A Schantl 1, Marcel Roza 1, Peter Van Kerkhof 1, Ger J Strous 1
PMCID: PMC1223864  PMID: 14519102

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.

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Selected References

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