Linked Life Data

12960054

Source:http://linkedlifedata.com/resource/pubmed/id/12960054

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2003-9-22
pubmed:abstractText
Little is known of the normal physiological processes that govern the cell surface residency of the human follitropin receptor (hFSHR), a G protein-coupled receptor expressed in the ovary and testis. In the hFSHR, the third intracellular (3i) loop is considered to be pivotal in attenuation of ligand activation, particularly internalization. To gain a better understanding of these processes, we used a yeast-based interaction trap to identify cytoplasmic proteins in a human ovarian cDNA library that interacted with the hFSHR 3i loop. Among the cDNA identified, four encoded isoforms of ubiquitin. Immunoprecipitated hFSHR probed with an antiubiquitin antibody revealed that the receptor is ubiquitinated, although not exclusively on the 3i loop. Cell-surface hFSHR levels increased when expressed at nonpermissive temperature in a temperature-sensitive, ubiquitination-defective cell line. Similarly, after treatment with proteasome inhibitors, HEK293 cells stably transfected with an hFSHR expression plasmid showed an increase in follitropin binding. Proteasome inhibitors did not affect the rate of FSH internalization when receptors were saturated before internalization was measured. In contrast, internalization decreased when binding experiments were performed under nonequilibrium conditions. A mutant hFSHR-K555R, which removes the only lysine in the 3i loop available for ubiquitination, was still ubiquitinated, illustrating that, although the third loop enables and interaction with ubiquitin, it is not the sole site of ubiquitination. These observations are consistent with a role for ubiquitination in the regulation of hFSHR cell surface residency. Additionally, it can be inferred that a sequence in the 3i loop is involved in regulating receptor ubiquitination and internalization.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
144
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4393-402
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Regulation of follitropin receptor cell surface residency by the ubiquitin-proteasome pathway.
pubmed:affiliation
Laboratory of Clinical and Experimental Endocrinology and Immunology, Division of Molecular Medicine, Wadsworth Center, New York State Department of Health, Albany, New York 12208, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't