Trafficking regulator of GLUT4-1 (TRARG1) is a GSK3 substrate.
Trafficking regulator of GLUT4-1 (TRARG1) is a GSK3 substrate.
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GLUT4-1的运输调节因子(TRARG1)是GSK3底物。
DOI：
10.1042/bcj20220153
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发表时间：
2022-06-17
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GLUT 4 -1的运输调节因子TRARG 1正向调节胰岛素刺激的GLUT 4运输和胰岛素敏感性。然而，这种情况发生的机制仍不清楚。使用生物化学和质谱分析，我们发现TRARG 1以PI 3 K/Akt依赖性方式响应胰岛素而去磷酸化，并且是GSK 3的新底物。在丝氨酸84处引发鼠TRARG 1的磷酸化允许在丝氨酸72、76和80处进行GSK 3指导的磷酸化。在人TRARG 1中观察到类似的磷酸化模式，表明我们的发现可翻译为人TRARG 1。药理学抑制GSK 3增加细胞表面GLUT 4在细胞刺激与次最大剂量的胰岛素，这是受损后Trarg 1敲低，表明TRARG 1作为GSK 3介导的调节剂在GLUT 4运输。这些数据将TRARG 1置于胰岛素信号网络中，并提供了对GSK 3如何调节脂肪细胞中GLUT 4运输的见解。
Trafficking regulator of GLUT4-1, TRARG1, positively regulates insulin-stimulated GLUT4 trafficking and insulin sensitivity. However, the mechanism(s) by which this occurs remain(s) unclear. Using biochemical and mass spectrometry analyses we found that TRARG1 is dephosphorylated in response to insulin in a PI3K/Akt-dependent manner and is a novel substrate for GSK3. Priming phosphorylation of murine TRARG1 at serine 84 allows for GSK3-directed phosphorylation at serines 72, 76 and 80. A similar pattern of phosphorylation was observed in human TRARG1, suggesting that our findings are translatable to human TRARG1. Pharmacological inhibition of GSK3 increased cell surface GLUT4 in cells stimulated with a submaximal insulin dose, and this was impaired following Trarg1 knockdown, suggesting that TRARG1 acts as a GSK3-mediated regulator in GLUT4 trafficking. These data place TRARG1 within the insulin signaling network and provide insights into how GSK3 regulates GLUT4 trafficking in adipocytes.