Source:http://linkedlifedata.com/resource/pubmed/id/16302975
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
23
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| pubmed:dateCreated |
2005-11-23
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| pubmed:abstractText |
SOCS3 is a negative regulator of cytokine signalling that inhibits Janus kinase-signal transduction and activator of transcription (JAK-STAT) mediated signal tranduction by binding to phosphorylated tyrosine residues on intracellular subunits of various cytokine receptors, as well as possibly the JAK proteins. SOCS3 consists of a short N-terminal sequence followed by a kinase inhibitory region, an extended SH2 domain and a C-terminal suppressor of cytokine signalling (SOCS) box. SOCS3 and the related protein, cytokine-inducible SH2-containing protein, are unique among the SOCS family of proteins in containing a region of mostly low complexity sequence, between the SH2 domain and the C-terminal SOCS box. Using NMR, we assigned and determined the secondary structure of a murine SOCS3 construct. The SH2 domain, unusually, consists of 140 residues, including an unstructured insertion of 35 residues. This insertion fits the criteria for a PEST sequence and is not required for phosphotyrosine binding, as shown by isothermal titration calorimetry. Instead, we propose that the PEST sequence has a functional role unrelated to phosphotyrosine binding, possibly mediating efficient proteolytic degradation of the protein. The latter half of the kinase inhibitory region and the entire extended SH2 subdomain form a single alpha-helix. The mapping of the true SH2 domain, and the location of its C terminus more than 50 residues further downstream than predicted by sequence homology, explains a number of previously unexpected results that have shown the importance of residues close to the SOCS box for phosphotyrosine binding.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
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| pubmed:issn |
1742-464X
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
272
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
6120-30
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| pubmed:meshHeading |
pubmed-meshheading:16302975-Amino Acid Sequence,
pubmed-meshheading:16302975-Animals,
pubmed-meshheading:16302975-Cloning, Molecular,
pubmed-meshheading:16302975-Humans,
pubmed-meshheading:16302975-Mice,
pubmed-meshheading:16302975-Molecular Sequence Data,
pubmed-meshheading:16302975-Nuclear Magnetic Resonance, Biomolecular,
pubmed-meshheading:16302975-Phosphotyrosine,
pubmed-meshheading:16302975-Protein Structure, Secondary,
pubmed-meshheading:16302975-Sequence Alignment,
pubmed-meshheading:16302975-Signal Transduction,
pubmed-meshheading:16302975-Suppressor of Cytokine Signaling Proteins,
pubmed-meshheading:16302975-src Homology Domains
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| pubmed:year |
2005
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| pubmed:articleTitle |
Secondary structure assignment of mouse SOCS3 by NMR defines the domain boundaries and identifies an unstructured insertion in the SH2 domain.
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| pubmed:affiliation |
Walter and Eliza Hall Institute, Parkville, Victoria, Australia. babon@wehi.edu.au
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| pubmed:publicationType |
Journal Article
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