Blockade of growth hormone receptor shedding by a metalloprotease inhibitor

Endocrinology
J AleleS J Frank

Abstract

GH, an important growth-promoting and metabolic hormone, exerts its biological effects by interacting with cell surface GH receptors (GHRs). The GHR is a single membrane-spanning protein that binds GH via its extracellular domain. The high affinity GH-binding protein (GHBP), which corresponds to a soluble form of the GHR extracellular domain, carries a substantial fraction of the GH in the circulation of various species and probably has a role in modulation of the hormone's bioavailability. Although in rodents, it is believed that the GHBP is largely derived by translation of an alternatively spliced GHR messenger RNA, in humans and rabbits, proteolytic cleavage of the membrane-anchored receptor releases the GHR extracellular domain, which is believed to thereby become the GHBP. In this study, we used human IM-9 lymphocytes and GHR antibodies to study this proteolytic shedding of the GHBP. As determined by immunoblotting with anti-GHR cytoplasmic domain serum, addition of phorbol 12-myristate 13-acetate (PMA; 1 microg/ml) to serum-starved cells led to rapid loss (roughly 60% decline after 1 h; t(1/2) = approximately 5 min) of mature GHRs (115-140 kDa) from either total cell or detergent-soluble extracts. Loss of full-length GHR...Continue Reading

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Citations

May 27, 2010·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Kazutaka HayashidaPyong Woo Park
Apr 15, 2016·Molecular Endocrinology·Yue ZhangStuart J Frank
Mar 19, 2002·Endocrinology·Peter van KerkhofGer J Strous
Jul 15, 2006·Molecular Endocrinology·Samantha L Gadd, Charles V Clevenger
Sep 5, 2014·Molecular Endocrinology·Ying LiuStuart J Frank
Nov 17, 2009·Science in China. Series C, Life Sciences·ZhiYong LiaoMingJiang Wu
Dec 13, 2003·Endocrine Reviews·Stephanie R EdmondsonChristopher J Wraight
Sep 12, 2014·Molecular Endocrinology·Yujun GanStuart J Frank
Aug 18, 2000·The Journal of Clinical Endocrinology and Metabolism·M BallesterosK K Ho
Dec 19, 2002·The Journal of Biological Chemistry·Ralph GraichenPeter E Lobie
Apr 20, 2001·The Journal of Biological Chemistry·Y ZhangS J Frank
Mar 4, 2005·The Journal of Biological Chemistry·Jon W CowanStuart J Frank
May 9, 2000·The Journal of Biological Chemistry·P ReddyR A Black
Aug 25, 2020·Molecular and Cellular Endocrinology·Stuart J Frank
Sep 26, 2000·Molecular Genetics and Metabolism·J J Kopchick, J M Andry
Aug 10, 2001·Cellular Signalling·T ZhuP E Lobie
Dec 12, 2001·Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society·S J Frank
Jul 1, 2008·Biochimica Et Biophysica Acta·Stuart J Frank, Serge Y Fuchs
Apr 26, 2011·Biochemical and Biophysical Research Communications·Xiangdong WangStuart J Frank

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