Suppressors of cytokine signaling (SOCS): inhibitors of the JAK/STAT pathway.
The suppressors of cytokine signaling (SOCS) are recently identified inhibitors of cytokine and growth factor (GF) signaling that act via the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway. Cytokine-mediated JAK/STAT signaling controls a number of important biologic responses, including immune function, cellular growth, differentiation, and hematopoieses. The SOCS family consists of eight proteins: CIS and SOCS1-SOCS7, which contain a central SH2 domain, a conserved C-terminus referred to as the SOCS box, and a unique N-terminus. The expression of SOCS-1 to -3 and CIS is induced by cytokine or GF stimulation, resulting in the inhibition of JAK/STAT-mediated cytokine signaling by what appears to be a classic negative feedback loop. In this article we review cytokine/GF signaling by the JAK/STAT pathway, discovery of the SOCS family, the regulation of SOCS expression, mechanism(s) of SOCS action, and we summarize some of the biochemical and genetic studies investigating the physiologic role of SOCS in regulating cytokine activity.
Cooney
Robert N
RN
Department of Surgery, The Pennsylvania State University College of Medicine, Hershey 17033, USA.
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D016207:Cytokines / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D053613:Janus Kinase 1; D005810:Multigene Family; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011506:Proteins / Q000502:physiology; D012097:Repressor Proteins; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000378:metabolism*
D002352:Carrier Proteins; D016207:Cytokines; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D012097:Repressor Proteins; C108944:SOCS1 protein, human; C408990:SOCS5 protein, human; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; D053613:Janus Kinase 1