Linked Life Data

20554759

Source:http://linkedlifedata.com/resource/pubmed/id/20554759

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2010-7-30
pubmed:abstractText
Naturally ligand independent constitutively active gp130 variants were described to be responsible for inflammatory hepatocellular adenomas. Recently, we genetically engineered a ligand-independent constitutively active gp130 variant based on homodimerization of Jun leucine zippers. Because also heterodimeric complexes within the gp130 family may have tumorigenic potential, we seek to generate ligand-independent constitutively active heterodimers for all known gp130-receptor complexes based on IL-15/IL-15R alpha-sushi fusion proteins. Ligand-independent heterodimerization of gp130 with WSX-1, LIFR, and OSMR and of OSMR with GPL led to constitutive, ligand-independent STAT1 and/or STAT3 and ERK1/2 phosphorylation. Moreover, these receptor combinations induced transcription of the STAT3 target genes c-myc and Pim-1 and factor-independent growth of stably transduced Ba/F3-gp130 cells. Here, we establish the IL-15/IL-15R alpha-sushi system as a new system to mimic constitutive and ligand-independent activation of homo- and heterodimeric receptor complexes, which might be applicable to other heterodimeric receptor families. A mutated IL-15 protein, which was still able to bind the IL-15R alpha-sushi domain, but not to beta- and gamma-receptor chains, in combination with the 2A peptide technology may be used to translate our in vitro data into the in vivo situation to assess the tumorigenic potential of gp130-heterodimeric receptor complexes.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1939-4586
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2797-807
pubmed:dateRevised
2011-8-4
pubmed:meshHeading
pubmed-meshheading:20554759-Animals, pubmed-meshheading:20554759-Cattle, pubmed-meshheading:20554759-Cell Line, pubmed-meshheading:20554759-Cell Proliferation, pubmed-meshheading:20554759-Cytokine Receptor gp130, pubmed-meshheading:20554759-Cytokines, pubmed-meshheading:20554759-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:20554759-Humans, pubmed-meshheading:20554759-Interleukin-15, pubmed-meshheading:20554759-Interleukin-15 Receptor alpha Subunit, pubmed-meshheading:20554759-Ligands, pubmed-meshheading:20554759-Mice, pubmed-meshheading:20554759-Multiprotein Complexes, pubmed-meshheading:20554759-Protein Multimerization, pubmed-meshheading:20554759-STAT Transcription Factors, pubmed-meshheading:20554759-Signal Transduction, pubmed-meshheading:20554759-Transcription, Genetic
pubmed:year
2010
pubmed:articleTitle
Forced homo- and heterodimerization of all gp130-type receptor complexes leads to constitutive ligand-independent signaling and cytokine-independent growth.
pubmed:affiliation
*Department of Biochemistry, Christian-Albrechts-Universität, D-24098 Kiel, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't