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Linkage of the ubiquitin‐conjugating system and the endocytic pathway in ligand‐induced internalization of the growth hormone receptor
Author(s) -
Govers Roland,
van Kerkhof Peter,
Schwartz Alan L.,
Strous Ger J.
Publication year - 1997
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/16.16.4851
Subject(s) - biology , internalization , endocytic cycle , linkage (software) , ubiquitin , microbiology and biotechnology , growth hormone receptor , receptor , ligand (biochemistry) , growth hormone , endocytosis , genetics , biochemistry , hormone , gene
The major function of the ubiquitin‐conjugating system is the targeting of cytosolic and nuclear proteins for degradation by the proteasome. Recently, ubiquitin conjugation has been implicated in the downregulation of signalling receptors such as the mammalian growth hormone receptor (GHR) and the α‐factor receptor in yeast. By examining truncated receptors, the internalization‐deficient receptor mutant F327A and conditions under which clathrin‐mediated GHR endocytosis is inhibited, we show here that GHR ubiquitination and ligand‐induced GHR internalization are coupled events. Previously, we had shown that GHR endocytosis is dependent on an intact ubiquitination system. Here we present evidence that GHR ubiquitination depends on an intact endocytic pathway. Our data indicate that the ubiquitin‐conjugating system and the endocytic pathway interact at the cytoplasmic tail of the GHR at the plasma membrane, where they cooperate to regulate internalization of the GHR.