The C-terminus of CIS defines its interaction pattern.
Biochem J
; 401(1): 257-67, 2007 Jan 01.
Article
en En
| MEDLINE
| ID: mdl-16961462
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Proteínas Supresoras de la Señalización de Citocinas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Biochem J
Año:
2007
Tipo del documento:
Article
País de afiliación:
Bélgica