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T Bellido CA O'Brien PK Roberson SC Manolagas 《Canadian Metallurgical Quarterly》1998,273(33):21137-21144
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S Akira 《Canadian Metallurgical Quarterly》1997,29(12):1401-1418
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SE Nicholson TA Willson A Farley R Starr JG Zhang M Baca WS Alexander D Metcalf DJ Hilton NA Nicola 《Canadian Metallurgical Quarterly》1999,18(2):375-385
SOCS-1 (suppressor of cytokine signaling-1) is a representative of a family of negative regulators of cytokine signaling (SOCS-1 to SOCS-7 and CIS) characterized by a highly conserved C-terminal SOCS box preceded by an SH2 domain. This study comprehensively examined the ability of several SOCS family members to negatively regulate the gp130 signaling pathway. SOCS-1 and SOCS-3 inhibited both interleukin-6 (IL-6)- and leukemia inhibitory factor (LIF)-induced macrophage differentiation of murine monocytic leukemic M1 cells and LIF induction of a Stat3-responsive reporter construct in 293T fibroblasts. Deletion of amino acids 51-78 in the N-terminal region of SOCS-1 prevented inhibition of LIF signaling. The SOCS-1 and SOCS-3 N-terminal regions were functionally interchangeable, but this did not extend to other SOCS family members. Mutation of SH2 domains abrogated the ability of both SOCS-1 and SOCS-3 to inhibit LIF signal transduction. Unlike SOCS-1, SOCS-3 was unable to inhibit JAK kinase activity in vitro, suggesting that SOCS-1 and SOCS-3 act on the JAK-STAT pathway in different ways. Thus, although inhibition of signaling by SOCS-1 and SOCS-3 requires both the SH2 and N-terminal domains, their mechanisms of action appear to be biochemically different. 相似文献
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Specific inhibition of Stat3 signal transduction by PIAS3 总被引:1,自引:0,他引:1
CD Chung J Liao B Liu X Rao P Jay P Berta K Shuai 《Canadian Metallurgical Quarterly》1997,278(5344):1803-1805
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