Negative regulators of cytokine signaling.
The interaction of a cytokine with its specific cell surface receptor triggers the activation of intracellular signaling pathways that ultimately program the cellular response. Although the specific components and actions of the pathways driving these responses, such as the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway, are relatively well defined, it is becoming clear that important mechanisms exist to restrain these signaling cascades. This review discusses the key biochemical actions and biological roles of the phosphatase SHP-1, the protein inhibitors of activated STATs (PIAS) and the suppressor of cytokine signaling (SOCS) protein family in the negative regulation of cytokine signal transduction.
Kile
B T
BT
Division of Cancer and Hematology, The Walter and Eliza Hall Institute for Medical Research and The Cooperative Research Centre for Cellular Growth Factors, Royal Melbourne Hospital, Victoria, Australia. kile@wehi.edu.au
Nicola
N A
NA
Alexander
W S
WS
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology; D016207:Cytokines / Q000502:physiology*; D004268:DNA-Binding Proteins; D019281:Dimerization; D004789:Enzyme Activation; D005786:Gene Expression Regulation / Q000502:physiology; D018390:Gene Targeting; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008954:Models, Biological; D010766:Phosphorylation; D050828:Protein Inhibitors of Activated STAT; D011499:Protein Processing, Post-Translational; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011506:Proteins / Q000235:genetics / Q000502:physiology; D012097:Repressor Proteins; D015398:Signal Transduction / Q000502:physiology*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors / Q000502:physiology; D018909:src Homology Domains
D002352:Carrier Proteins; D016207:Cytokines; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C494211:Pias1 protein, mouse; D050828:Protein Inhibitors of Activated STAT; D011506:Proteins; D012097:Repressor Proteins; C108944:SOCS1 protein, human; C106643:SOCS2 protein, human; C106644:SOCS3 protein, human; C491590:Socs1 protein, mouse; C491409:Socs2 protein, mouse; C491411:Socs3 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D011505:Protein-Tyrosine Kinases; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C509248:Ptpn6 protein, mouse