The C-terminus of CIS defines its interaction pattern

Delphine Lavens , Peter Ulrichts , Dominiek Catteeuw , Kris Gevaert , Joël Vandekerckhove , Frank Peelman , Sven Eyckerman , Jan Tavernier (1)

1 Flanders interuniversity Institute for Biotechnology, Department of Medical Protein Research, Faculty of Medicine and Health Sciences

Proteins of the Suppressors of Cytokine Signaling (SOCS) family are characterised by a conserved modular structure with pre-SH2, SH2 and SOCS-box domains. Several members including CIS, SOCS1 and SOCS3 are rapidly induced 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) 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 adaptor MyD88. Mutagenesis revealed that one single tyrosine at position 253 is a critical binding determinant. Much in contrast, substrate binding by the highly related SOCS2 protein, and also by SOCS1 and SOCS3, does not require their SOCS-box.

Mots clés: Life Sciences

Delphine Lavens, Peter Ulrichts, Dominiek Catteeuw, Kris Gevaert, Joël Vandekerckhove, et al.. The C-terminus of CIS defines its interaction pattern. Biochemical Journal, 2006, 401 (1), pp.257-267. ⟨10.1042/BJ20060242⟩. ⟨hal-00478533⟩