Suppressors of cytokine signalling and regulation of growth hormone action.
The Suppressors of Cytokine Signalling (SOCS) are a family of proteins that are produced in response to signals from a diverse range of cytokines and growth factors and which act to attenuate cytokine signal transduction. Members of the SOCS family form a classical negative feedback loop with key actions involving inhibition of the Janus Kinase-Signal Transducers and Activators of Transcription (JAK-STAT) signalling cascade. Extensive analyses have implicated each of CIS, SOCS1, SOCS2 and SOCS3 in the regulation of Growth Hormone (GH) signal transduction. The expression of each of these SOCS proteins is induced in cells stimulated with GH and their over-expression in cell lines blocks aspects of GH signalling. In vivo studies with genetically modified mice have confirmed important physiological roles for SOCS proteins in regulation of GH action. In particular, mice lacking SOCS2 display gigantism accompanied by evidence of deregulated GH signalling. A precise understanding of the actions of SOCS proteins in GH signalling may offer new opportunities for therapeutic intervention in growth disorders and other conditions involving GH action.
Greenhalgh
Christopher J
CJ
Division of Cancer and Haematology, The Walter and Eliza Hall Institute of Medical Research and the Cooperative Research Centre for Cellular Growth Factors, 1G Royal Parade, Parkville, Vic. 3050, Australia.
Alexander
Warren S
WS
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D013006:Growth Hormone / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D016207:Cytokines; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; C491589:Socs1 protein, rat; C491408:Socs2 protein, rat; C491410:Socs3 protein, rat; 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; D013006:Growth Hormone; D011505:Protein-Tyrosine Kinases