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-α-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–GHR2 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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January 2004
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Research Article|
January 15 2004
The growth hormone receptor interacts with its sheddase, the tumour necrosis factor-alpha-converting enzyme (TACE)
Julia A. SCHANTL;
Julia A. SCHANTL
Department of Cell Biology, University Medical Center Utrecht, AZU G02.525, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
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Marcel ROZA;
Marcel ROZA
Department of Cell Biology, University Medical Center Utrecht, AZU G02.525, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
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Peter van KERKHOF;
Peter van KERKHOF
Department of Cell Biology, University Medical Center Utrecht, AZU G02.525, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
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Ger J. STROUS
Ger J. STROUS
1
Department of Cell Biology, University Medical Center Utrecht, AZU G02.525, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
1To whom correspondence should be addressed (e-mail strous@med.uu.nl).
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Publisher: Portland Press Ltd
Received:
August 29 2003
Revision Received:
September 22 2003
Accepted:
September 30 2003
Accepted Manuscript online:
September 30 2003
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2004
2004
Biochem J (2004) 377 (2): 379–384.
Article history
Received:
August 29 2003
Revision Received:
September 22 2003
Accepted:
September 30 2003
Accepted Manuscript online:
September 30 2003
Citation
Julia A. SCHANTL, Marcel ROZA, Peter van KERKHOF, Ger J. STROUS; The growth hormone receptor interacts with its sheddase, the tumour necrosis factor-alpha-converting enzyme (TACE). Biochem J 15 January 2004; 377 (2): 379–384. doi: https://doi.org/10.1042/bj20031321
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