Linked Life Data

10566591

Source:http://linkedlifedata.com/resource/pubmed/id/10566591

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1999-12-6
pubmed:abstractText
Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8) encodes a structural and functional homologue of human IL-6 called viral IL-6 (vIL-6). Expression of vIL-6 in KSHV-related lymphoproliferative disorders has been implicated in their pathogenesis. vIL-6 has been shown to mimic a number of IL-6 activities including stimulating the growth of IL-6 dependent cell lines and activating the JAK1 and STAT1/3 pathway in HepG2 cells. However, IL-6 and vIL-6 display differences in receptor usage that may give rise to underlying qualitative and quantitative differences in the signaling pathways utilized. While IL-6 has an absolute requirement for both the IL-6 Ralpha and the gp130 subunits, vIL-6 appears to require only gp130. In addition to JAK1 and STAT1/3 pathways, IL-6 activates multiple other pathways including the direct activation of STAT 5 by JAK1, the Ras-MAP kinase cascade and a novel H7-sensitive pathway. In this study we examined whether vIL-6 is capable of signaling via distinct IL-6 response elements (IL-6 RE) under the control of these different pathways. We show that vIL-6 activates both STAT1/3- and STAT5-dependent Type II IL-6 REs. In addition, vIL-6 induces transcriptional activation via a Type I IL-6 RE that binds C/EBP, indicative of Ras-MAP kinase pathway induction. Furthermore, vIL-6 is capable of activating the IL-6 response element in the c-jun promoter (RE-IL-6). vIL-6 induced activation of JRE-IL-6 requires both the Ets- and Cre-like sites, suggesting that vIL-6 is capable of stimulating the same novel serine/threonine kinase mediated pathway as IL-6. These results demonstrate that vIL-6 can stimulate all of the known IL-6-induced signaling pathways. Therefore, vIL-6 could potentially contribute to KSHV-related disease progression by continued activation of IL-6-stimulated growth and anti-apoptotic pathways even when cells attempt to protect themselves from IL-6 over-stimulation by downmodulating their IL-6Ralpha subunits.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0198-8859
pubmed:author
pubmed:issnType
Print
pubmed:volume
60
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
921-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10566591-CCAAT-Enhancer-Binding Proteins, pubmed-meshheading:10566591-DNA-Binding Proteins, pubmed-meshheading:10566591-Gene Expression Profiling, pubmed-meshheading:10566591-Herpesvirus 8, Human, pubmed-meshheading:10566591-Humans, pubmed-meshheading:10566591-Interleukin-6, pubmed-meshheading:10566591-Leukocytes, Mononuclear, pubmed-meshheading:10566591-MAP Kinase Signaling System, pubmed-meshheading:10566591-Models, Genetic, pubmed-meshheading:10566591-Nuclear Proteins, pubmed-meshheading:10566591-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:10566591-Protein Binding, pubmed-meshheading:10566591-Response Elements, pubmed-meshheading:10566591-Signal Transduction, pubmed-meshheading:10566591-Transcription Factors, pubmed-meshheading:10566591-Tumor Cells, Cultured, pubmed-meshheading:10566591-Viral Proteins
pubmed:year
1999
pubmed:articleTitle
KSHV-encoded viral IL-6 activates multiple human IL-6 signaling pathways.
pubmed:affiliation
Department of Pathology, Columbia University College of Physicians and Surgeons, New York, NY 10027, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.