Suppressors of cytokine signaling: Relevance to gastrointestinal function and disease.
OBJECTIVE
The suppressor of cytokine signaling (SOCS) proteins are a family of Src homology 2 domain-containing proteins. Currently, there are 8 members of the SOCS family, of which a number have been implicated strongly in the negative regulation of cytokine signal transduction pathways.


METHODS
This review focuses on recent discoveries about 4 SOCS family members, SOCS-1, -2, and -3, and cytokine-inducible SH2-domain containing (CIS), and provides more limited information about other SOCS family members.


RESULTS
A large number of cytokines and growth factors are now known to induce SOCS proteins. In turn, SOCS inhibit the actions of a growing number of cytokines and growth factors in vitro or in vivo. SOCS proteins exert their inhibitory effects at the level of activation of janus kinases (JAKs) or by competing with transcription factors for binding sites on activated cytokine receptors. SOCS proteins also may mediate the ubiquitination and subsequent degradation of the SOCS protein and its bound signaling complex. Genetic modification of SOCS genes in mice has revealed crucial roles in the negative regulation of a number of important physiologic parameters including interferon gamma activity, growth, blood cell production, and placental development.


CONCLUSIONS
Information about SOCS action in gastrointestinal function and disease is only just emerging, but available data indicate a role in growth of gastrointestinal tissues, inflammatory bowel disease, and cancer.
Greenhalgh
Christopher J
CJ
Cancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research and the Cooperative Research Centre for Cellular Growth Factors, Royal Melbourne Hospital, Australia.
Miller
Megan E
ME
Hilton
Douglas J
DJ
Lund
P Kay
PK
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D004268:DNA-Binding Proteins; D004068:Digestive System Physiological Phenomena; D005767:Gastrointestinal Diseases / Q000503:physiopathology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins / Q000502:physiology*; D012097:Repressor Proteins; 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
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D017874:Immediate-Early Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D012097:Repressor Proteins; 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; C108944:SOCS1 protein, human; C106643:SOCS2 protein, human; C106644:SOCS3 protein, human