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 prot eins (GH-BPs), with molecular weights of 60 and 55 kDa were found to b e constitutively released from human IM-9 cells. The release of the GH -BPs was not inhibited by inhibitors of protein synthesis (cycloheximi de) and transport (brefeldin A). Down-regulation by human growth hormo ne or trypsin pretreatment of surface growth hormone receptors abolish ed the GH-BP release, suggesting that cell-surface human growth hormon e receptors are involved in the GH-BP release, Several inhibitors of s erine-, thiol-, and acid-proteases did not affect the GH-BP release, E DTA efficiently blocked the GH-BP release, This inhibition by EDTA was restored by addition of Mg2+ and Co2+. These results suggest that hum an GH-BPs are constitutively released by proteolytic cleavage of cell- surface growth hormone receptors by a metalloprotease.