Insulin-induced insulin receptor substrate-1 degradation is mediated by the proteasome degradation pathway
Insulin-induced insulin receptor substrate-1 degradation is mediated by the proteasome degradation pathway
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DOI：
10.2337/diabetes.48.7.1359
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发表时间：
1999-07-01
期刊：
影响因子：
7.7
通讯作者：
Mitchell, JJ
中科院分区：
文献类型：
--
作者：
Sun, XJ;Goldberg, JL;Mitchell, JJ
胰岛素受体底物(IRS)蛋白是介导胰岛素受体酪氨酸激酶信号转导的重要细胞内分子。在动物、人类和培养的细胞中，在各种条件下，胰岛素抵抗状态下IRS蛋白的含量都有所下降。然而，控制细胞IRS蛋白水平的分子机制尚不清楚。我们报道，慢性胰岛素治疗诱导培养细胞中IRS-1蛋白的降解，但不能诱导IRS-2蛋白的降解。胰岛素诱导的IRS-1的降解可以被蛋白酶体降解的特异性抑制剂lactacystin所阻止，这些数据首次证明了胰岛素诱导的IRS-1的降解是由蛋白酶体降解途径介导的。IRS-2可以逃脱胰岛素诱导的蛋白酶体降解，这表明这一降解过程存在特定的结构要求。
Insulin receptor substrate (IRS) proteins are important intracellular molecules that mediate insulin receptor tyrosine kinase signaling. A decreased content of IRS proteins has been found in insulin-resistant states in animals, humans, and cultured cells under various conditions. However, the molecular mechanism that controls cellular levels of IRS proteins is unknown. We report that chronic insulin treatment induces the degradation of IRS-1, but not IRS-2, protein in cultured cells. The insulin-induced degradation of IRS-1 can be prevented by pretreatment with lactacystin, a specific inhibitor for proteasome degradation, These data demonstrate, for the first time, that insulin-induced degradation of IRS-1 is mediated by the proteasome degradation pathway. IRS-2 can escape from the insulin-induced proteasome degradation, suggesting the existence of specific structural requirements for this degradation process.