Proteomic analysis of protein palmitoylation in adipocytes.
Proteomic analysis of protein palmitoylation in adipocytes.
复制标题
脂肪细胞中蛋白质棕榈酰化的蛋白质组学分析。
作者：
Ren W;Jhala US;Du K
蛋白质棕榈酰化通过调节蛋白质与细胞膜之间的动态相互作用，参与了广泛的生物过程，包括蛋白质转运、分选、亚膜分配、蛋白质-蛋白质相互作用和细胞信号转导。为了探讨蛋白质棕榈酰化在脂肪细胞中的作用，我们对脂肪组织和3T3-L1脂肪细胞中的棕榈酰化蛋白质进行了蛋白质组学分析，并鉴定了800多个可能的棕榈酰化蛋白质。这些包括各种转运蛋白、脂肪和葡萄糖代谢所需的酶、蛋白质运输的调节器和信号分子。值得注意的是，参与葡萄糖转运蛋白GLUT4膜转运的关键蛋白IRAP、Munc18c、AS160和GLUT4，以及JAK-STAT通路中的信号蛋白JAK1和2，JAK-STAT中的STAT1、3和5A和SHP2，在培养的脂肪细胞和原代脂肪组织中被棕榈酰化。进一步的研究表明，肥胖时GLUT4和IRAP的棕榈酰化发生了改变，而JAK1的棕榈酰化在JAK1的细胞内定位中起着调节作用。总体而言，我们的研究提供了证据，表明蛋白质棕榈酰化在脂肪细胞功能中具有新的和潜在的调节作用。
Protein palmitoylation, by modulating the dynamic interaction between protein and cellular membrane, is involved in a wide range of biological processes, including protein trafficking, sorting, sub-membrane partitioning, protein-protein interaction and cell signaling. To explore the role of protein palmitoylation in adipocytes, we have performed proteomic analysis of palmitoylated proteins in adipose tissue and 3T3-L1 adipocytes and identified more than 800 putative palmitoylated proteins. These include various transporters, enzymes required for lipid and glucose metabolism, regulators of protein trafficking and signaling molecules. Of note, key proteins involved in membrane translocation of the glucose-transporter Glut4 including IRAP, Munc18c, AS160 and Glut4, and signaling proteins in the JAK-STAT pathway including JAK1 and 2, STAT1, 3 and 5A and SHP2 in JAK-STAT, were palmitoylated in cultured adipocytes and primary adipose tissue. Further characterization showed that palmitoylation of Glut4 and IRAP was altered in obesity, and palmitoylation of JAK1 played a regulatory role in JAK1 intracellular localization. Overall, our studies provide evidence to suggest a novel and potentially regulatory role for protein palmitoylation in adipocyte function.