Back to Search Start Over

The C-terminus of CIS defines its interaction pattern.

Authors :
Lavens D
Ulrichts P
Catteeuw D
Gevaert K
Vandekerckhove J
Peelman F
Eyckerman S
Tavernier J
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.

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