Suppressors of cytokine signaling proteins in innate and adaptive immune responses.
Suppressors of cytokine signaling (SOCS) proteins have been identified as important mediators of negative regulatory circuits within cytokine receptor signaling. They are induced upon stimulation by an increasing set of cytokines as well as further immunological stimuli and are capable to inhibit Janus kinases and signal transducer and activator of transcription signaling. Inhibition is mediated by interfering directly with signal transduction at the receptor as well as targeting of associated molecules for proteosomal degradation. Targeted gene deletion approaches have revealed the importance of SOCS mediated termination of cytokine signaling during normal cellular activation. In addition to their function as classical feedback inhibitors SOCS proteins display a broad panel of inhibitory activity thereby mediating cross-talk modulation between different stimuli. The consequences for regulation of innate and adaptive immune responses are thus obvious. Finally, there are emerging data showing involvement of SOCS proteins in various immune diseases. Modulating SOCS activity could be a promising new approach for molecular therapeutic strategies.
Dalpke
Alexander
A
Institute of Medical Microbiology and Hygiene, Philipps-University, Marburg, Germany. dalpke@mailer.uni-marburg.de
Heeg
Klaus
K
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000502:physiology*; D005246:Feedback; D006801:Humans; D007113:Immunity, Innate; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D018345:Mice, Knockout; D008957:Models, Genetic; D011506:Proteins / Q000276:immunology*; D018121:Receptors, Cytokine / Q000502:physiology; D012097:Repressor Proteins; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins
D002352:Carrier Proteins; D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D018121:Receptors, Cytokine; D012097:Repressor Proteins; C108944:SOCS1 protein, human; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins