Linked Life Data

9178752

Source:http://linkedlifedata.com/resource/pubmed/id/9178752

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1997-9-23
pubmed:abstractText
Transient transfection experiments in which three different estrogen response element-containing reporter genes were cotransfected into HeLa cells, together with constitutively expressed estrogen receptor (ER) constructs, demonstrate that activation of the transcription of the reporter genes by epidermal growth factor (EGF) and by cholera toxin with 3-isobutyl-1-methyl-xanthine, which elevate cellular cAMP, is dependent upon the presence of functional ER. Cotransfection of the reporter genes with truncated versions of the ER shows that the two non-ligand activators of ER require different regions of the receptor to produce their effects on transcription. EGF acts primarily by means of transactivation domain AF-1, whereas cAMP acts via transactivation domain AF-2 of the ER. A point mutation that removes a major site of inducible phosphorylation within the AF-1 domain of the ER abolishes the response to EGF, but the response to estradiol and cAMP is retained. Specific inhibition of cAMP-activated protein kinase (protein kinase A) prevents the response to elevated cAMP but does not affect EGF or estradiol responses. Overexpression of the protein kinase A catalytic subunit in HeLa cells results in an amplified response to estradiol, similar to that induced by cholera toxin with 3-isobutyl-1-methyl-xanthine. Comparable experiments performed using COS-1 cells produce similar results but also reveal cell type- and promoter-specific aspects of the activation mechanisms. Apparently, the ER may be activated by three different signal molecules, estradiol, EGF, and cAMP, each using a mechanism that is distinguishable from that of the others.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0888-8809
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
928-37
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:9178752-1-Methyl-3-isobutylxanthine, pubmed-meshheading:9178752-Animals, pubmed-meshheading:9178752-COS Cells, pubmed-meshheading:9178752-Cyclic AMP, pubmed-meshheading:9178752-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:9178752-Enzyme Inhibitors, pubmed-meshheading:9178752-Epidermal Growth Factor, pubmed-meshheading:9178752-Estradiol, pubmed-meshheading:9178752-Gene Expression Regulation, Developmental, pubmed-meshheading:9178752-Genes, Reporter, pubmed-meshheading:9178752-HeLa Cells, pubmed-meshheading:9178752-Humans, pubmed-meshheading:9178752-Isoquinolines, pubmed-meshheading:9178752-Point Mutation, pubmed-meshheading:9178752-Promoter Regions, Genetic, pubmed-meshheading:9178752-Receptors, Estrogen, pubmed-meshheading:9178752-Sulfonamides, pubmed-meshheading:9178752-Transcriptional Activation, pubmed-meshheading:9178752-Transfection
pubmed:year
1997
pubmed:articleTitle
Two separate mechanisms for ligand-independent activation of the estrogen receptor.
pubmed:affiliation
School of Biological Sciences, University of Liverpool, United Kingdom.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't