Cleavage of growth hormone by rabbit liver plasmalemma enhances binding.
Several studies have shown that proteolytic cleavage can enhance the biological activity of the growth hormone (GH) molecule. It seemed possible, therefore, that proteolytic modification of GH might be a normal function of GH-target tissues. Plasmalemma-enriched fractions isolated from rabbit liver were found to contain a proteinase(s) which cleaves the large disulfide loop of human and rat GH. The proteolytic activity was specific to plasmalemma-enriched fractions in that much lower activities were observed in microsomal-enriched fractions prepared from the same livers. The plasmalemmal proteinase(s) may be a trypsin-like enzyme because proteolytic activity was decreased by two serine proteinase inhibitors. Inhibition by unlabeled human GH of 125I-GH binding to receptors did not prevent cleavage of the tracer; therefore, hormone-receptor interaction was not required for cleavage of the GH molecule. In binding studies, cleaved GH associated more readily than did intact hormone with rabbit liver receptors. These studies suggest that plasmalemma-enriched fractions prepared from rabbit liver contain a proteinase which cleaves the GH molecule in a highly specific manner. Moreover, it is unlikely that inactivation of GH is the function of this limited proteolysis because cleaved hormone is bound preferentially by at least a subset of receptors in rabbit liver.
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D010450:Endopeptidases / Q000378:metabolism*; D013006:Growth Hormone / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007457:Iodine Radioisotopes; D008099:Liver / Q000378:metabolism*; D008970:Molecular Weight; D011485:Protein Binding; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011986:Receptors, Somatotropin; D013045:Species Specificity
D007457:Iodine Radioisotopes; D011956:Receptors, Cell Surface; D011986:Receptors, Somatotropin; D013006:Growth Hormone; D010450:Endopeptidases