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rdf:type |
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lifeskim:mentions |
umls-concept:C0079189,
umls-concept:C0086982,
umls-concept:C0110279,
umls-concept:C0205199,
umls-concept:C0205369,
umls-concept:C0376315,
umls-concept:C0449432,
umls-concept:C0755506,
umls-concept:C0908711,
umls-concept:C1179435,
umls-concept:C1514873,
umls-concept:C1524073,
umls-concept:C1548799,
umls-concept:C1705248,
umls-concept:C2003941
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pubmed:issue |
25
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pubmed:dateCreated |
2001-6-18
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pubmed:abstractText |
Ciliary neurotrophic factor (CNTF) is a cytokine supporting the differentiation and survival of a number of neural cell types. Its receptor complex consists of a ligand-binding component, CNTF receptor (CNTFR), associated with two signaling receptor components, gp130 and leukemia inhibitory factor receptor (LIFR). Striking phenotypic differences between CNTF- and CNTFR-deficient mice suggest that CNTFR serves as a receptor for a second developmentally important ligand. We recently demonstrated that cardiotrophin-like cytokine (CLC) associates with the soluble orphan receptor cytokine-like factor-1 (CLF) to form a heterodimeric cytokine that displayed activities only on cells expressing the tripartite CNTF receptor on their surface. In this present study we examined the membrane binding of the CLC/CLF composite cytokine and observed a preferential interaction of the cytokine with the CNTFR subunit. Signaling pathways recruited by the CLC/CLF complex in human neuroblastoma cell lines were also analyzed in detail. The results obtained showed an activation of Janus kinases (JAK1, JAK2, and TYK2) leading to a tyrosine phosphorylation of the gp130 and LIFR. The phosphorylated signaling receptors served in turn as docking proteins for signal transducing molecules such as STAT3 and SHP-2. In vitro analysis revealed that the gp130-LIFR pathway could also stimulate the phosphatidylinositol 3-kinase and the mitogen-activated protein kinase pathways. In contrast to that reported before for CNTF, soluble CNTFR failed to promote the action CLC/CLF, and an absolute requirement of the membrane form of CNTFR was required to generate a functional response to the composite cytokine. This study reinforces the functional similarity between CNTF and the CLC/CLF composite cytokine defining the second ligand for CNTFR.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/PTPN11 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/PTPN6 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatase...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatase...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Ciliary Neurotrophic...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytokine,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/STAT3 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/cardiotrophin 1,
http://linkedlifedata.com/resource/pubmed/chemical/cytokine-like factor-1
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
22
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pubmed:volume |
276
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
22476-84
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11294841-Animals,
pubmed-meshheading:11294841-COS Cells,
pubmed-meshheading:11294841-Cytokines,
pubmed-meshheading:11294841-DNA-Binding Proteins,
pubmed-meshheading:11294841-Humans,
pubmed-meshheading:11294841-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:11294841-MAP Kinase Signaling System,
pubmed-meshheading:11294841-Protein Tyrosine Phosphatase, Non-Receptor Type 11,
pubmed-meshheading:11294841-Protein Tyrosine Phosphatase, Non-Receptor Type 6,
pubmed-meshheading:11294841-Protein Tyrosine Phosphatases,
pubmed-meshheading:11294841-Protein-Serine-Threonine Kinases,
pubmed-meshheading:11294841-Proto-Oncogene Proteins,
pubmed-meshheading:11294841-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:11294841-Receptor, Ciliary Neurotrophic Factor,
pubmed-meshheading:11294841-Receptors, Cytokine,
pubmed-meshheading:11294841-STAT1 Transcription Factor,
pubmed-meshheading:11294841-STAT3 Transcription Factor,
pubmed-meshheading:11294841-Signal Transduction,
pubmed-meshheading:11294841-Trans-Activators,
pubmed-meshheading:11294841-Tumor Cells, Cultured
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pubmed:year |
2001
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pubmed:articleTitle |
Signaling pathways recruited by the cardiotrophin-like cytokine/cytokine-like factor-1 composite cytokine: specific requirement of the membrane-bound form of ciliary neurotrophic factor receptor alpha component.
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pubmed:affiliation |
INSERM EMI-9928, CHU d'Angers, 4 rue Larrey, 49003 Angers, France and the Centre d'Immunologie Pierre Fabre, 5 avenue Napoléon III, 74164 Saint Julien en Genevois, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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