Growth hormone induces detergent insolubility of gh receptors in
im-9 cells.
Goldsmith, Jeffrey F., Sung Joong Lee, Jing Jiang, and Stuart J.
Frank.
Department of Medicine, Division of Endocrinology and Metabolism,
and the Departments of Cell Biology and Pathology, University of
Alabama at Birmingham, and the Veterans Affairs Medical Center4,
Birmingham, AL 35294
APStracts 4:0171E, 1997.
In this study, we examined human growth hormone (hGH)-induced changes
in nonionic detergent solubility characteristics of its receptor
(hGHR). Exposure of IM-9 cells to hGH caused a time- and
concentration-dependent loss of immunoblottable detergent-extractable
hGHRs and a corresponding accumulation of receptors in a detergent
-insoluble pool. At 37oC, both the loss of detergent-soluble and the
accumulation of detergent-insoluble hGHRs both preceded hGH-induced
loss of total cell hGHRs. The detergent-insoluble receptor pool was
progressively enriched in an apparent disulfide-linked form of the
hGHR. Exposure to hGH at 4oC allowed hGH-induced hGHR disulfide
linkage, but did not promote changes in receptor detergent
solubility, indicating that hGHR detergent insolubility cannot be
explained solely by the formation of that linkage. Experiments
carried out with hGH at 20oC with the phorbol ester, phorbol-12,13
-myristate acetate (PMA) at 37oC, indicated that loss of detergent
-soluble hGHRs can be uncoupled from accumulation of detergent
-insoluble receptors. From these data, we envision at least two
related, but separable, trafficking pathways taken by hGHRs after
their surface interaction with hGH -- (1) ligand-mediated endocytosis
and degradation (accounting for only some of the receptors lost from
the detergent-soluble fraction); and (2) ligand-mediated accumulation
in a detergent-insoluble subcellular fraction (arising largely from
receptors redistributed from the detergent-soluble fraction).
Received 16 April 1997; accepted in final form 24 July 1997.
APS Manuscript Number E174-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 27 August 1997