The conserved SOCS box motif in suppressors of cytokine signaling binds toelongins B and C and may couple bound proteins to proteasomal degradation

The suppressors of cytokine signaling (SOCS) family of proteins act as intr acellular inhibitors of several cytokine signal transduction pathways. Thei r expression is induced by cytokine activation of the Janus kinase/signal t ransducer and activator of transcription (JAK/STAT) pathway and they act as a negative feedback loop by subsequently inhibiting the JAK/STAT pathway e ither by direct interaction with activated JAKs or with the receptors, Thes e interactions are mediated at least in part by the SH2 domain of SOCS prot eins but these proteins also contain a highly conserved C-terminal homology domain termed the SOCS box. Here we show that the SOCS box mediates intera ctions with elongins B and C, which in turn may couple SOCS proteins and th eir substrates to the proteasomal protein degradation pathway. Analogous to the family of F-box-containing proteins, it appears that the SOCS proteins may act as adaptor molecules that target activated cell signaling proteins to the protein degradation pathway.