Synip phosphorylation does not regulate insulin-stimulated GLUT4 translocation.
Synip phosphorylation does not regulate insulin-stimulated GLUT4 translocation.
复制标题
Synip 磷酸化不调节胰岛素刺激的 GLUT4 易位。
DOI：
10.1016/j.bbrc.2005.05.027
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发表时间：
2005
影响因子：
3.1
通讯作者：
Lienhard,GustavE
中科院分区：
文献类型：
--
作者：
Sano,Hiroyuki;Kane,Susan;Sano,Eiko;Lienhard,GustavE
胰岛素导致葡萄糖转运蛋白 GLUT4 从细胞内位置快速易位到脂肪和肌肉细胞的质膜。有大量证据表明，这一运输过程的信号传导位于胰岛素激活蛋白激酶 Akt 的下游。连接信号传导与运输的一种 Akt 底物是 Rab 的 160kDa GTP 酶激活蛋白。另一个潜在的连接底物是蛋白质 Synip，它与 SNARE syntaxin4 结合。最近的一项研究提供了证据，证明 Akt 在丝氨酸 99 上磷酸化 Synip（至少在体外），并提出这种磷酸化通过导致 Synip 与 Syntaxin4 解离来实现 GLUT4 易位。在本研究中，我们发现缺乏该磷酸化位点的 Synip 突变体 S99A 的显着过度表达对 3T3-L1 脂肪细胞中胰岛素刺激的 GLUT4 易位没有影响。这一发现有力地证明了 GLUT4 易位不需要 Synip 丝氨酸 99 上的磷酸化。
Insulin causes the rapid translocation of the glucose transporter GLUT4 from intracellular sites to the plasma membrane in fat and muscle cells. There is considerable evidence that the signaling to this trafficking process is downstream of the insulin-activated protein kinase Akt. One Akt substrate that connects signaling to trafficking is a 160kDa GTPase activating protein for Rabs. Another potential connecting substrate is the protein Synip, which associates with the SNARE syntaxin4. A recent study presents evidence that Akt phosphorylates Synip on serine 99, at least in vitro, and proposes that this phosphorylation enables GLUT4 translocation by causing the dissociation of Synip from syntaxin4. In the present study we show that marked overexpression of Synip mutant S99A, which lacks this phosphorylation site, has no effect on insulin-stimulated GLUT4 translocation in 3T3-L1 adipocytes. This finding is strong evidence that phosphorylation of Synip on serine 99 is not required for GLUT4 translocation.