Linked Life Data

9584216

Source:http://linkedlifedata.com/resource/pubmed/id/9584216

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1998-6-18
pubmed:abstractText
Gonadotropin-independent, male-limited precocious puberty is caused by a variety of mutations in the lutropin/choriogonadotropin receptor (LHR) that produce constitutive receptor activation. Two of these mutations encode replacement of conserved aspartate residues at positions 564 and 578 with glycine. We previously used site-directed mutagenesis to study the functional role of the Asp578 side chain in transmembrane helix 6, and concluded that it is its ability to serve as a properly positioned interhelical hydrogen bond acceptor, rather than its negative charge, that is important for stabilizing the inactive state of the LHR. We now report the effects of substituting seven different amino acids for the Asp564 residue located at the carboxyl terminus of the third intracellular loop. Glycine, alanine, valine, leucine, phenylalanine, and asparagine produced constitutive activation in a COS-7 cell expression system (3-5-fold increase in basal cAMP), but glutamate did not, indicating that a negative charge at position 564 may be important for maintaining the inactive LHR conformation. Characterization of double-mutant receptors showed that certain substitutions at Asp564 and Asp578 have a cumulative effect on basal receptor activity, perhaps because they mimic different aspects of the activation process normally triggered by hormone binding.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
894-901
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
An anionic residue at position 564 is important for maintaining the inactive conformation of the human lutropin/choriogonadotropin receptor.
pubmed:affiliation
Department of Laboratory Medicine, Kyoto University School of Medicine, Kyoto 606-8507, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't