Linked Life Data

20083850

Source:http://linkedlifedata.com/resource/pubmed/id/20083850

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2010-1-19
pubmed:abstractText
Previously, using cultured human epidermal keratinocytes we have demonstrated that the activity of CRF1 receptor can be modulated by the process of alternative splicing. This phenomenon has been further investigated in the mouse corticotroph AtT-20 cell line. In the cells, transiently transfected with the plasmids coding human CRF1 isoforms, only isoforms alpha and c have shown expression on the cell membrane. Other isoforms d, e, g and h had intracellular localization with the isoform e also found in the nucleus. Co-expression of the CRF1alpha (main form of the receptor) with isoforms d, f and g prevented its expression on the cell surface resulting in accumulation of CRF1alpha inside of the cell. s expected, CRF stimulated time and dose dependent activation of CRE, CARE, AP-1 transcription elements and POMC promoter in AtT-20 cells overexpressing human CRF1alpha, while having no effect on the AP-1 transcriptional activity in cells transfected with other isoforms (d, f, g and h). However, when cells were co-transfected with CRF1alpha and CRF1e or h the CRF stimulated transcriptional activity of CRE and AP-1 was amplified in comparison to the cells expressing solely CRF1alpha; the effect was more pronounced for CRF1h than for CRF1e. In contrast, the conditioned media from the cells overexpressing CRF1e and h inhibited the CRF induced transcriptional activity in cells overexpressing CRF1alpha. Media from cells expressing CRF1h were significantly more potent that from cells transfected with CRF1e. In summary, we have demonstrated that alternatively spliced CRF1 isoforms can regulate the cellular localization of CRF1alpha, and that soluble CRF1 isoforms can have a dual effect on CRF1alpha activity depending on the intracellular vs. extracellular localization.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1899-1505
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
60 Suppl 4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
39-46
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Modulation of corticotropin releasing factor (CRF) signaling through receptor splicing in mouse pituitary cell line AtT-20--emerging role of soluble isoforms.
pubmed:affiliation
Department of Molecular Enzymology, Intercollegiate Faculty of Biotechnology of University of Gdansk and Medical University of Gdansk, Gdansk, Poland.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural