TIMP3 Modulates GHR Abundance and GH Sensitivity

Published on Jun 1, 2016in Molecular Endocrinology3.628
· DOI :10.1210/me.2015-1302
Yue Zhang15
Estimated H-index: 15
(UAB: University of Alabama at Birmingham),
Xiangdong Wang16
Estimated H-index: 16
(SDU: Shandong University)
+ 4 AuthorsStuart J. Frank45
Estimated H-index: 45
(UAB: University of Alabama at Birmingham)
GH receptor (GHR) binds GH at the cell surface via its extracellular domain and initiates intracellular signal transduction, resulting in important anabolic and metabolic actions. GH signaling is subject to dynamic regulation, which in part is exerted by modulation of cell surface GHR levels. Constitutive and inducible metalloprotease-mediated cleavage of GHR regulate GHR abundance and thereby modulate GH action. We previously demonstrated that GHR proteolysis is catalyzed by the TNF-α converting enzyme (TACE; ADAM17). Tissue inhibitors of metalloproteases-3 (TIMP3) is a natural specific inhibitor of TACE, although mechanisms underlying this inhibition are not yet fully understood. In the current study, we use two model cell lines to examine the relationships between cellular TACE, TIMP3 expression, GHR metalloproteolysis, and GH sensitivity. These two cell lines exhibited markedly different sensitivity to inducible GHR proteolysis, which correlated directly to their relative levels of mature TACE vs unpr...
  • References (78)
  • Citations (4)
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