The suppressor of cytokine signaling (SOCS) 1 and SOCS3 but not SOCS2 proteins inhibit interferon-mediated antiviral and antiproliferative activities

The suppressor of cytokine signaling (SOCS) proteins are a family of cytoki ne-inducible negative regulators of cytokine signaling. Interferon (IFN)-ga mma treatment induces the expression of SOCS1, SOCS2, and SOCS3 mRNAs. To e xamine the effect of SOCS proteins on IFN-mediated Janus-activated kinase/s ignal transducers and activators of transcription (STAT) signaling, HeLa- a nd MCF-7-derived stable cell lines expressing SOCS1, SOCS2, and SOCS3 prote ins were established, SOCS1 and SOCS3 but not SOCS2 inhibited the tyrosine phosphorylation and nuclear translocation of STAT1 in response to IFN stimu lation. The IFN-mediated antiviral and antiproliferative activities were co nsistently blocked by the constitutive expression of SOCS1 and SOCS3 but no t SOCS2 proteins. The maximum inhibitory activities of SOCS1 and SOCS3 prot eins toward the activation of STAT1 were observed at very low levels of SOC S protein expression. In addition, SOCS1 exhibited a much stronger inhibito ry activity toward the activation of STAT1 than did SOCS3, These results su ggest that SOCS1 and SOCS3 but not SOCS2 are inhibitors of IFN-mediated Jan us-activated kinase/STAT signaling pathways.