Linked Life Data

18079192

Source:http://linkedlifedata.com/resource/pubmed/id/18079192

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-2-22
pubmed:abstractText
To identify genes that are most responsive to a sustained activation of a G(s) protein-coupled receptor, HEK293 cells were stably transfected with the beta(2)-adrenergic receptor and stimulated with agonist isoproterenol (1 mum). A microarray study indicated that the gene with the highest stimulation index (500-fold) encoded the common alpha-subunit of human glycoprotein hormones (GPHalpha). Induction of GPHalpha transcription in response to cAMP elevations resulted in a dramatic increase (600-fold) of protein secretion as shown by RT-PCR and a highly specific time-resolved immunofluorometric assay. Cloning and sequencing of the GPHalpha cDNA and mass spectrometric analysis of HPLC-purified GPHalpha derived from serum-free HEK293-beta(2)-adrenergic receptor-stimulated cells verified the nature of the molecule. Enzymatic deglycosylation with subsequent Western blots revealed that this was a large hyperglycosylated form of GPHalpha that had not been associated with a beta-subunit previously. This uncombined variant is known to be either cosecreted with GPHs from the pituitary, the placenta, and a variety of tumors or secreted without GPHs from APUD cells and rare tumors. Moreover, it is similar to GPHalpha found at high concentrations in seminal plasma. As shown by a panel of endogenous or transfected G protein-coupled receptors in HEK293 cells, the expression of large GPHalpha was controlled by G(s)- and G(q)- but not G(i)-dependent receptors and mediated via cAMP and Ca(++) release. This suggests that Gq- or G(s)-coupled receptors other than the classical GnRH receptor may play a role in the regulation of nonpituitary, nonplacental GPHalpha secretion under physiological and pathological conditions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
149
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1144-54
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18079192-Adrenergic beta-Agonists, pubmed-meshheading:18079192-Amino Acid Sequence, pubmed-meshheading:18079192-Base Sequence, pubmed-meshheading:18079192-Calcium, pubmed-meshheading:18079192-Cell Line, pubmed-meshheading:18079192-Cyclic AMP, pubmed-meshheading:18079192-GTP-Binding Protein alpha Subunits, Gq-G11, pubmed-meshheading:18079192-GTP-Binding Protein alpha Subunits, Gs, pubmed-meshheading:18079192-Glycoprotein Hormones, alpha Subunit, pubmed-meshheading:18079192-Gonadotropin-Releasing Hormone, pubmed-meshheading:18079192-Humans, pubmed-meshheading:18079192-Isoproterenol, pubmed-meshheading:18079192-Kidney, pubmed-meshheading:18079192-Molecular Sequence Data, pubmed-meshheading:18079192-Receptors, Adrenergic, beta-2, pubmed-meshheading:18079192-Receptors, LHRH, pubmed-meshheading:18079192-Transcription, Genetic, pubmed-meshheading:18079192-Transfection
pubmed:year
2008
pubmed:articleTitle
Non-gonadotropin-releasing hormone-mediated transcription and secretion of large human glycoprotein hormone alpha-subunit in human embryonic kidney-293 cells.
pubmed:affiliation
Department of Pharmacology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
pubmed:publicationType
Journal Article