PMID: 11312156Apr 20, 2001Paper

Shedding of growth hormone-binding protein is inhibited by hydroxamic acid-based protease inhibitors: proposed mechanism of activation of growth hormone-binding protein secretase

The Journal of Endocrinology
T AmitR J Barkey

Abstract

The present study describes events postulated to be involved in the regulated mechanism of proteolytic shedding of growth hormone (GH)-binding protein (GHBP). Using Chinese hamster ovary (CHO) cell lines stably transfected either with the full-length human GH receptor (hGHR) or with the cytoplasmic domain-truncated hGHR (hGHR(tr)), we show that the phorbol ester, phorbol 12-myristate 13-acetate (PMA), caused a rapid time- and dose-dependent increase in GHBP secretion, which, as expected, was matched by a corresponding decrease in cell-surface GHR. Furthermore, PMA equally enhanced GHBP release from CHO/hGHR(tr) cells, suggesting that the cytoplasmic domain of hGHR is not essential for PMA-induced shedding. PMA is known to specifically activate protein kinase C and, indeed, the stimulatory effects of PMA in both cell lines were completely inhibited by the protein kinase inhibitor, staurosporine (100 nM), suggesting that activation of protein kinase C (PKC) may mediate PMA-induced GHBP shedding. Since proteolytic cleavage of several cell-surface proteins was shown to be stimulated by modulators of PKC activity and inhibited by metalloprotease inhibitors, we studied the effects of two hydroxamic acid-based inhibitors of zinc-depen...Continue Reading

Citations

Jan 31, 2004·Biochemical and Biophysical Research Communications·Anthony J ChubbEdward D Sturrock
Apr 23, 2003·Molecular and Cellular Endocrinology·Peter van KerkhofGer J Strous
Apr 4, 2002·Biological Chemistry·Persio Dello Sbarba, Elisabetta Rovida
Jan 12, 2002·Biochemical and Biophysical Research Communications·Françoise ConteEric Bieth
Jun 15, 2007·Critical Reviews in Biochemistry and Molecular Biology·Bénédicte CauweGhislain Opdenakker
Aug 1, 2007·Journal of Thrombosis and Haemostasis : JTH·M C BerndtR K Andrews
May 28, 2011·Biochimica Et Biophysica Acta·Darío FernándezMatilde S Ayuso
Apr 28, 2007·Arteriosclerosis, Thrombosis, and Vascular Biology·Robert K AndrewsMichael C Berndt
Mar 4, 2005·The Journal of Biological Chemistry·Jon W CowanStuart J Frank
Dec 10, 2015·British Journal of Pharmacology·Stephen Ph AlexanderCgtp Collaborators
Feb 20, 2004·American Journal of Physiology. Cell Physiology·Nina L TsakadzeStanley E D'Souza
Jul 15, 2003·The Journal of Biological Chemistry·Ishrut HussainColin Dingwall

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