He Fang, Stephens Jacqueline M
Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA.
Biochem Biophys Res Commun. 2006 May 26;344(1):95-8. doi: 10.1016/j.bbrc.2006.03.142. Epub 2006 Mar 30.
Insulin receptor substrate (IRS)-1 is a key protein in insulin signaling. Several studies have shown that the expression of IRS-1 can be modulated by protein degradation via the proteasome and the degradation of IRS-1 can be related to insulin-resistant states. The degradation of IRS-1 has been shown to be induced by SOCS-1 and SOCS-3 via the ubiquitin pathway. The goal of our study was to determine if the induction of SOCS-3 correlated with increased IRS-1 degradation in cultured 3T3-L1 adipocytes. Interestingly, our studies have shown that there is little correlation between the induction in SOCS-3 expression and the degradation of IRS-1 in mature 3T3-L1 adipocytes. Our results clearly demonstrate that treatment with leukemia inhibitory factor (LIF) or cardiotrophin (CT)-1 strongly induces the expression of SOCS-3 in mature 3T3-L1 adipocytes, but does not affect the degradation of IRS-1. On the contrary, tumor necrosis factor (TNF) alpha and insulin, which very weakly induce SOCS-3 expression, have profound effects on IRS-1 degradation. In summary, our results indicate that the expression of SOCS-3 does not correlate with the degradation of IRS-1 proteins in fat cells.
胰岛素受体底物（IRS）-1是胰岛素信号传导中的关键蛋白。多项研究表明，IRS-1的表达可通过蛋白酶体介导的蛋白质降解进行调节，且IRS-1的降解可能与胰岛素抵抗状态相关。已有研究显示，SOCS-1和SOCS-3可通过泛素途径诱导IRS-1的降解。我们研究的目的是确定在培养的3T3-L1脂肪细胞中，SOCS-3的诱导是否与IRS-1降解增加相关。有趣的是，我们的研究表明，在成熟的3T3-L1脂肪细胞中，SOCS-3表达的诱导与IRS-1的降解之间几乎没有相关性。我们的结果清楚地表明，用白血病抑制因子（LIF）或心肌营养素（CT）-1处理可强烈诱导成熟3T3-L1脂肪细胞中SOCS-3的表达，但不影响IRS-1的降解。相反，肿瘤坏死因子（TNF）α和胰岛素虽只能微弱地诱导SOCS-3表达，却对IRS-1降解有显著影响。总之，我们的结果表明，SOCS-3的表达与脂肪细胞中IRS-1蛋白的降解不相关。
