Proteasome inhibitor enhances growth hormone-binding protein release.
We used murine Ba/F3 cells transfected with human growth hormone receptor (hGHR) cDNA to investigate the regulatory mechanisms of human growth hormone-binding protein (hGH-BP) release. The extracellular domain of hGHRs were cleaved and released as hGH-BPs (a soluble form of hGHR). The hGH-BP release was enhanced by phorbol 12,13-dibutyrate (PDBu), and suggested to be mediated by activation of PKC, the same as in human IM-9 cells. Thus, Ba/F3 cells have hGH-BP-releasing pathways similar to those of human cells. The proteasome inhibitors MG-132 and clasto-lactacystin beta-lactone also increased hGH-BP release from Ba/F3-hGHR cells, and MG-132 and PDBu synergistically increased hGH-BP release. The results obtained by using three PKC inhibitors Gö 6976, GF 109203X and Gö 6983 suggest that the enhancement of hGH-BP release by MG-132 and PDBu is mediated by different mechanisms probably involving different PKC isozymes.
Takagi
K
K
Division of Biochemistry and Immunochemistry, National Institute of Health Sciences, Setagaya, Tokyo 158-8501, Japan.
Saito
Y
Y
Sawada
J
J
D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D007976:Leupeptins / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects
D002352:Carrier Proteins; D015853:Cysteine Proteinase Inhibitors; D007527:Isoenzymes; D007976:Leupeptins; D008565:Membrane Proteins; D009097:Multienzyme Complexes; C405010:delta-hGHR; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde; C051815:somatotropin-binding protein