Linked Life Data

12950268

Source:http://linkedlifedata.com/resource/pubmed/id/12950268

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
2003-9-2
pubmed:abstractText
Activating mutations of the thyroid-stimulating hormone receptor (TSHr) have been identified as a cause of toxic adenomas. Germline-inactivating TSHr mutations have been described as a cause of congenital hypothyroidism. The effects of combining activating and inactivating mutations within a single receptor was studied. The double mutant T477I/P639S contained an activating TSHr mutation (P639S) together with an inactivating one (T477I). The other one (I486M/P639S) contained two activating mutations. Constructs were expressed in COS-7 cells and basal and TSH-stimulated cyclic AMP (cAMP) accumulation and inositol phosphate (IP) production were determined. The expression at the cell surface was studied both with binding and fluorescence-activated cell scanning analysis. Our results show that the effect of combining the two activating mutations is an increase in the constitutive activity only for the cAMP pathway and not for the IP pathway suggesting that different mutations result in receptor conformations with different relative abilities to couple to Gs-alpha or Gq-alpha. Surprisingly the double mutant containing the T477I behaves as an activating receptor with constitutive activity both for the cAMP and IP pathways. These data show that an inactive form of the TSHr which is trapped inside a cell after transfection is able to gain the membrane surface when combined with an activated form of the receptor.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0014-2956
pubmed:author
pubmed:issnType
Print
pubmed:volume
270
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3839-47
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12950268-Amino Acid Substitution, pubmed-meshheading:12950268-Animals, pubmed-meshheading:12950268-COS Cells, pubmed-meshheading:12950268-Cyclic AMP, pubmed-meshheading:12950268-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:12950268-Flow Cytometry, pubmed-meshheading:12950268-Heterotrimeric GTP-Binding Proteins, pubmed-meshheading:12950268-Humans, pubmed-meshheading:12950268-Inositol Phosphates, pubmed-meshheading:12950268-Iodine Radioisotopes, pubmed-meshheading:12950268-Mutagenesis, Site-Directed, pubmed-meshheading:12950268-Protein Binding, pubmed-meshheading:12950268-Receptors, Cell Surface, pubmed-meshheading:12950268-Receptors, Thyrotropin, pubmed-meshheading:12950268-Recombinant Proteins, pubmed-meshheading:12950268-Thyrotropin, pubmed-meshheading:12950268-Transfection
pubmed:year
2003
pubmed:articleTitle
Proper targeting and activity of a nonfunctioning thyroid-stimulating hormone receptor (TSHr) combining an inactivating and activating TSHr mutation in one receptor.
pubmed:affiliation
Medicina del Lavoro, Università di Pisa, Pisa, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't