Release of a soluble form of growth hormone receptors (growth hormone-binding proteins) from human IM-9 cells by proteolytic cleavage.
Soluble forms of growth hormone receptors, growth hormone-binding proteins (GH-BPs), with molecular weights of 60 and 55kDa were found to be constitutively released from human IM-9 cells. The release of the GH-BPs was not inhibited by inhibitors of protein synthesis (cycloheximide) and transport (brefeldin A). Down-regulation by human growth hormone or trypsin pretreatment of surface growth hormone receptors abolished the GH-BP release, suggesting that cell-surface human growth hormone receptors are involved in the GH-BP release. Several inhibitors of serine-, thiol-, and acid-proteases did not affect the GH-BP release. EDTA efficiently blocked the GH-BP release. This inhibition by EDTA was restored by addition of Mg(2+) and Co(2+). These results suggest that human GH-BPs are constitutively released by proteolytic cleavage of cell-surface growth hormone receptors by a metalloprotease.
Saito
Y
Y
Division of Biochemistry and Immunochemistry, National Institute of Health Sciences, Tokyo.
Ikebuchi
H
H
Yamazaki
T
T
Sawada
J
J
D020126:Brefeldin A; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003517:Cyclopentanes / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012995:Solubility
D002352:Carrier Proteins; D003517:Cyclopentanes; D011480:Protease Inhibitors; D011500:Protein Synthesis Inhibitors; D020126:Brefeldin A; D003513:Cycloheximide; D010447:Peptide Hydrolases; C051815:somatotropin-binding protein