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The C-terminus of CIS defines its interaction pattern.
- Source :
-
The Biochemical journal [Biochem J] 2007 Jan 01; Vol. 401 (1), pp. 257-67. - Publication Year :
- 2007
-
Abstract
- Proteins of the SOCS (suppressors of cytokine signalling) family are characterized by a conserved modular structure with pre-SH2 (Src homology 2), SH2 and SOCS-box domains. Several members, including CIS (cytokine-inducible SH2 protein), SOCS1 and SOCS3, are induced rapidly upon cytokine receptor activation and function in a negative-feedback loop, attenuating signalling at the receptor level. We used a recently developed mammalian two-hybrid system [MAPPIT (mammalian protein-protein interaction trap)] to analyse SOCS protein-interaction patterns in intact cells, allowing direct comparison with biological function. We find that, besides the SH2 domain, the C-terminal part of the CIS SOCS-box is required for functional interaction with the cytokine receptor motifs examined, but not with the N-terminal death domain of the TLR (Toll-like receptor) adaptor MyD88. Mutagenesis revealed that one single tyrosine residue at position 253 is a critical binding determinant. In contrast, substrate binding by the highly related SOCS2 protein, and also by SOCS1 and SOCS3, does not require their SOCS-box.
- Subjects :
- Animals
Base Sequence
Cell Line
Chromatography, Affinity
DNA Primers
DNA, Complementary genetics
Humans
Kidney
Mice
Molecular Sequence Data
Mutagenesis, Site-Directed
Peptide Fragments chemistry
Peptide Fragments genetics
Peptide Fragments metabolism
Phosphopeptides chemistry
Phosphopeptides isolation & purification
Recombinant Proteins chemistry
Recombinant Proteins metabolism
Suppressor of Cytokine Signaling Proteins genetics
Transfection
Suppressor of Cytokine Signaling Proteins chemistry
Suppressor of Cytokine Signaling Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1470-8728
- Volume :
- 401
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The Biochemical journal
- Publication Type :
- Academic Journal
- Accession number :
- 16961462
- Full Text :
- https://doi.org/10.1042/BJ20060242