Linked Life Data

14647450

Source:http://linkedlifedata.com/resource/pubmed/id/14647450

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2004-2-12
pubmed:abstractText
Receptor crosstalk is an emerging and recurrent theme in cytokine and growth factor signaling; however, insight into the mechanism(s) underlying these interactions remains limited. Recently, we reported that crosstalk occurs between ErbB3 and the interferon alpha (IFN-alpha) signaling complex in the myeloma cell line KAS-6/1 and that this crosstalk contributes to the regulation of cell proliferation. In this study, we examined the mechanism underlying the transactivation of ErbB3 in the IFN-alpha growth-responsive KAS-6/1 cells. The examination of IFN-alpha receptor 1 and 2 (IFNAR1 and IFNAR2) levels revealed that the KAS-6/1 cell line overexpresses IFNAR1 relative to other myeloma cell lines that are growth arrested by IFN-alpha. Subsequent investigation of Tyk2, which is constitutively associated with IFNAR1, demonstrated that Tyk2 activation is uniquely sustained in the KAS-6/1 cell line following IFN-alpha stimulation. Interestingly, silencing of Tyk2 expression via siRNA resulted in attenuation of ErbB3 transactivation. However, inhibition of Jak1 expression also decreased IFN-alpha-induced tyrosine phosphorylation of ErbB3. Finally, siRNA downregulation of Tyk2 and Jak1 was found to decrease IFN-alpha-stimulated proliferation. These findings validate our previous report of ErbB3 involvement in IFN-alpha-induced proliferation and further suggest that both Janus kinase members, Tyk2 and Jak1, play a role in the transactivation of ErbB3 in this model system.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1197-205
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:14647450-Base Sequence, pubmed-meshheading:14647450-Cell Division, pubmed-meshheading:14647450-DNA Replication, pubmed-meshheading:14647450-Gene Expression Regulation, Neoplastic, pubmed-meshheading:14647450-Humans, pubmed-meshheading:14647450-Interferon-alpha, pubmed-meshheading:14647450-Membrane Proteins, pubmed-meshheading:14647450-Multiple Myeloma, pubmed-meshheading:14647450-Protein-Tyrosine Kinases, pubmed-meshheading:14647450-RNA, Small Interfering, pubmed-meshheading:14647450-Receptor, Interferon alpha-beta, pubmed-meshheading:14647450-Receptor, erbB-3, pubmed-meshheading:14647450-Receptor Cross-Talk, pubmed-meshheading:14647450-Receptors, Interferon, pubmed-meshheading:14647450-Signal Transduction, pubmed-meshheading:14647450-Transfection, pubmed-meshheading:14647450-Tumor Cells, Cultured
pubmed:year
2004
pubmed:articleTitle
A role for Janus kinases in crosstalk between ErbB3 and the interferon-alpha signaling complex in myeloma cells.
pubmed:affiliation
Department of Immunology, Tumor Biology Program, Mayo Graduate and Medical Schools, Mayo Clinic/Foundation, Rochester, MN 55905, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.