Linked Life Data

7721840

Source:http://linkedlifedata.com/resource/pubmed/id/7721840

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
1995-5-23
pubmed:abstractText
Substitution of arginine for glycine at position 120 in native 22-kDa human growth hormone (hGH) results in an analogue, G120R, which is unable to dimerize the GH receptor and is widely used to probe the molecular mechanism of action of hGH. When acting on human GH receptors, G120R antagonizes several biological effects of hGH, but is itself inactive as an agonist. It has been reported that this mutant also antagonizes hGH activation of the rat or human prolactin (PRL) receptor in cell-based assays, with no agonist activity. We have now tested this mutant in a sensitive MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)-ESTA (eluted stain assay) bioassay using rat PRL receptors in the Nb2 cell line. We confirm that G120R acts as an efficient antagonist of native hGH, but show that it can also act as an agonist to generate intracellular signals leading to metabolic activation and proliferation of Nb2 cells. We have demonstrated an unusual sensitivity to the presence of zinc (Zn2+). In the absence of added Zn2+, G120R shows weak but full agonist activity in the bioassay, and this can be blocked by co-incubation with recombinant hGH-binding protein. G120R can therefore be utilized to discriminate between the molecular mechanisms of hGH interactions with its somatogenic and lactogenic receptors. Future studies with G120R in the rat may need to take account of its significant agonist effects on PRL receptors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
270
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9222-6
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
G120R, a human growth hormone antagonist, shows zinc-dependent agonist and antagonist activity on Nb2 cells.
pubmed:affiliation
Division of Molecular Pathology, Middlesex Hospital, London, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't