Adams T E, Hansen J A, Starr R, Nicola N A, Hilton D J, Billestrup N
Centre for Animal Biotechnology, University of Melbourne, Parkville, Victoria, Australia.
J Biol Chem. 1998 Jan 16;273(3):1285-7. doi: 10.1074/jbc.273.3.1285.
Four members (SOCS-1, SOCS-2, SOCS-3, and CIS) of a family of cytokine-inducible, negative regulators of cytokine receptor signaling have recently been identified. To address whether any of these genes are induced in response to growth hormone (GH), serum-starved 3T3-F442A fibroblasts were incubated with GH for various time points, and the expression of the SOCS gene family was analyzed by Northern blotting. GH stimulated the rapid, transient induction of SOCS-3 mRNA, peaking 30 min after the initiation of GH exposure and declining to basal levels by 2 h. Expression of the other SOCS genes (SOCS-1, SOCS-2, CIS) was also up-regulated by GH, although to a lesser extent than SOCS-3 and with differing kinetics. SOCS-3 expression was also strongly induced in 3T3-F442A cells treated with leukemia-inhibitory factor (LIF), with weaker induction of SOCS-1 and CIS being observed. The preferential induction of SOCS-3 mRNA was also observed in hepatic RNA isolated from the livers of mice that had received a single supraphysiological dose of GH intraperitoneally. Co-transfection studies revealed that constitutive expression of SOCS-1 and SOCS-3, but not SOCS-2 or CIS, blocked GH-induced transactivation of the GH-responsive serine protease inhibitor 2.1 gene promoter.
最近发现了一个细胞因子诱导的细胞因子受体信号负调控因子家族中的四个成员（SOCS-1、SOCS-2、SOCS-3和CIS）。为了确定这些基因中是否有任何一个是在生长激素（GH）刺激下诱导产生的，将血清饥饿的3T3-F442A成纤维细胞与GH在不同时间点孵育，并用Northern印迹法分析SOCS基因家族的表达。GH刺激了SOCS-3 mRNA的快速、短暂诱导，在GH暴露开始后30分钟达到峰值，并在2小时内降至基础水平。其他SOCS基因（SOCS-1、SOCS-2、CIS）的表达也被GH上调，尽管程度低于SOCS-3，且动力学不同。在用白血病抑制因子（LIF）处理的3T3-F442A细胞中，SOCS-3的表达也被强烈诱导，而SOCS-1和CIS的诱导较弱。在从腹腔内接受单次超生理剂量GH的小鼠肝脏中分离的肝RNA中也观察到了SOCS-3 mRNA的优先诱导。共转染研究表明，SOCS-1和SOCS-3的组成型表达，但不是SOCS-2或CIS，阻断了GH诱导的GH反应性丝氨酸蛋白酶抑制剂2.1基因启动子的反式激活。
