RESUMEN

The suppressors of cytokine signaling (SOCS) family of proteins act as intracellular inhibitors of several cytokine signal transduction pathways. Their expression is induced by cytokine activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway and they act as a negative feedback loop by subsequently inhibiting the JAK/STAT pathway either by direct interaction with activated JAKs or with the receptors. These interactions are mediated at least in part by the SH2 domain of SOCS proteins but these proteins also contain a highly conserved C-terminal homology domain termed the SOCS box. Here we show that the SOCS box mediates interactions with elongins B and C, which in turn may couple SOCS proteins and their 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.

Asunto(s)

Proteínas Portadoras/metabolismo , Cisteína Endopeptidasas/metabolismo , Citocinas/fisiología , Péptidos y Proteínas de Señalización Intracelular , Complejos Multienzimáticos/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Proteínas/metabolismo , Proteínas Represoras , Factores de Transcripción/metabolismo , Secuencia de Aminoácidos , Animales , Sitios de Unión , Proteínas Portadoras/química , Línea Celular , Elonguina , Humanos , Ratones , Modelos Químicos , Datos de Secuencia Molecular , Complejo de la Endopetidasa Proteasomal , Proteínas/química , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes/metabolismo , Transducción de Señal , Proteína 1 Supresora de la Señalización de Citocinas , Proteína 3 Supresora de la Señalización de Citocinas , Proteínas Supresoras de la Señalización de Citocinas , Transfección , Células Tumorales Cultivadas , Dominios Homologos src