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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2002-8-29
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pubmed:abstractText |
Interleukin-2 induces heterodimerization of the IL-2 receptor beta and gamma subunits. This study addresses a role of the Shb adapter protein in IL-2 receptor signaling in T and NK cells. The IL-2Rbeta and gamma chains were found to co-immunoprecipitate with Shb, when each alone was co-expressed with Shb in COS cells. Using fusion proteins, the Shb SH2 domain was found to associate in a phosphotyrosine-dependent manner with the IL-2 receptor beta and gamma subunits upon IL-2 stimulation in primary T cells and the NK cell line NK-92. The main binding site of the Shb SH2 domain was phosphorylated Tyr-510 in the IL-2Rbeta chain. Shb was also phosphorylated upon IL-2 stimulation when overexpressed together with IL-2Rbeta (in pre-B cells, which express the gamma chain constitutively). These cells were also less apoptotic in the presence of IL-2 than cells overexpressing a mutant Shb (with a defect SH2 domain) or cells expressing a mutant IL-2Rbeta, with the Shb binding sites mutated to phenylalanine (Y392F, Y510F). JAK1 and JAK3 were also found to associate with Shb, but in contrast to the Shb-IL-2 receptor association, JAK1 and 3 appear to associate with the proline-rich regions of Shb. In conclusion, Shb links the IL-2 receptor to other signaling proteins and mediates the regulation of apoptosis in the presence of IL-2.
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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/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD56,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/JAK1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/JAK3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Phenylalanine,
http://linkedlifedata.com/resource/pubmed/chemical/Proline,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SHB protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0006-291X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
30
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pubmed:volume |
296
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
929-36
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12200137-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:12200137-Animals,
pubmed-meshheading:12200137-Antigens, CD56,
pubmed-meshheading:12200137-Apoptosis,
pubmed-meshheading:12200137-Binding Sites,
pubmed-meshheading:12200137-COS Cells,
pubmed-meshheading:12200137-Cell Division,
pubmed-meshheading:12200137-Cell Line,
pubmed-meshheading:12200137-DNA,
pubmed-meshheading:12200137-Humans,
pubmed-meshheading:12200137-Janus Kinase 1,
pubmed-meshheading:12200137-Janus Kinase 3,
pubmed-meshheading:12200137-Killer Cells, Natural,
pubmed-meshheading:12200137-Mutation,
pubmed-meshheading:12200137-Peptide Biosynthesis,
pubmed-meshheading:12200137-Peptides,
pubmed-meshheading:12200137-Phenylalanine,
pubmed-meshheading:12200137-Phosphorylation,
pubmed-meshheading:12200137-Precipitin Tests,
pubmed-meshheading:12200137-Proline,
pubmed-meshheading:12200137-Protein Binding,
pubmed-meshheading:12200137-Protein Structure, Tertiary,
pubmed-meshheading:12200137-Protein-Tyrosine Kinases,
pubmed-meshheading:12200137-Proto-Oncogene Proteins,
pubmed-meshheading:12200137-Receptors, Interleukin-2,
pubmed-meshheading:12200137-Recombinant Fusion Proteins,
pubmed-meshheading:12200137-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:12200137-Signal Transduction,
pubmed-meshheading:12200137-T-Lymphocytes,
pubmed-meshheading:12200137-Transfection,
pubmed-meshheading:12200137-Tyrosine
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pubmed:year |
2002
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pubmed:articleTitle |
IL-2 receptor signaling through the Shb adapter protein in T and NK cells.
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pubmed:affiliation |
Department of Medical Cell Biology, Uppsala University, Biomedicum, Box 571, S-75123 Uppsala, Sweden. Cecilia.Lindholm@medcellbiol.uu.se
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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