NCBI Summary:
The protein encoded by this gene contains a SH2 domain and a SOCS box domain. The protein thus belongs to the cytokine-induced STAT inhibitor (CIS), also known as suppressor of cytokine signaling (SOCS) or STAT-induced STAT inhibitor (SSI), protein family. CIS family members are known to be cytokine-inducible negative regulators of cytokine signaling. The expression of this gene can be induced by IL2, IL3, GM-CSF and EPO in hematopoietic cells. Proteasome-mediated degradation of this protein has been shown to be involved in the inactivation of the erythropoietin receptor. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq]
General function
Comment
Cellular localization
Cytoplasmic
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Ovarian function
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Expression regulated by
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Ovarian localization
Luteal cells
Comment
Maximal expression of Suppressors of Cytokine Signalling (SOCS) in the rat ovary occurs in late pregnancy. Anderson S et al. Maintenance of the rodent corpus luteum during pregnancy requires prolactin-receptor (PRL-R) signal transduction via STAT5. At the end of pregnancy prostaglandin F2alpha (PGF2alpha) induces luteal regression through many mechanisms, including down-regulation of PRL-R signaling. We have previously shown that a PGF2alpha analog upregulates Suppressors of Cytokine Signaling (SOCS) proteins in the corpus luteum of Day 19 pregnant rats leading to reduced STAT5 signaling. Here we examined endogenous SOCS expression and STAT5 signaling in the rat ovary during normal pregnancy and luteolysis. The mRNA expression of SOCS1, SOCS2 and SOCS3 and related Cytokine-inducible SH2-containing protein (CIS) was low in early pregnancy (Day 7), but significantly increased at mid-pregnancy (Days 10 and 13) associated with increased endogenous tyrosine phosphorylation (TyrP) of STAT5. In support of the notion that these changes are due to increasing placental lactogen levels at this time, we found that treatment with exogenous prolactin on Day 7 increased TyrP of STAT5 and induced SOCS mRNA expression, except SOCS3. After mid-pregnancy, further significant increases in SOCS3 and CIS mRNA expression were observed. Such changes in mRNA expression correlated with protein levels, with protein levels of both SOCS3 and CIS being maximal in late pregnancy (Days 19 to 21). In addition a significant reduction in TyrP of STAT5 was first observed on Day 20, with a further substantial decrease on Day 21. Therefore these results are consistent with the hypothesis that increased SOCS expression in the rat ovary during late pregnancy reduces STAT5 signaling which may be important in PGF2alpha-induced luteolysis.