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The C-terminus of CIS defines its interaction pattern.

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.

SUBMITTER: Lavens D

PROVIDER: S-EPMC1698688 | biostudies-literature | 2007 Jan

REPOSITORIES: biostudies-literature

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The C-terminus of CIS defines its interaction pattern.

Lavens Delphine D Ulrichts Peter P Catteeuw Dominiek D Gevaert Kris K Vandekerckhove Joël J Peelman Frank F Eyckerman Sven S Tavernier Jan J

The Biochemical journal 20070101 1

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 ...[more]

PMID: 16961462

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The C-terminus of CIS defines its interaction pattern.

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The C-terminus of CIS defines its interaction pattern.

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