蛋白酪氨酸磷酸酶 1B 调节脂肪细胞 SNARE 相互作用蛋白 Munc18c 的酪氨酸磷酸化。

Regulation of the SNARE-interacting protein Munc18c tyrosine phosphorylation in adipocytes by protein-tyrosine phosphatase 1B.

机构信息

Nutrition Department, University of California Davis, One Shields Ave, 3135 Meyer Hall, Davis, CA 95616, USA.

出版信息

Cell Commun Signal. 2013 Aug 12;11:57. doi: 10.1186/1478-811X-11-57.

BACKGROUND

Protein-tyrosine phosphatase 1B (PTP1B) is a physiological regulator of insulin signaling and adiposity and is a drug target for the treatment of obesity and diabetes. The molecular mechanisms underlying PTP1B metabolic actions require additional investigation.

RESULTS

Herein, we identify Munc18c as a novel PTP1B substrate in adipocytes and in vivo. We demonstrate nutritional regulation of Munc18c in adipose tissue revealing decreased expression upon high fat feeding. In addition, PTP1B deficiency leads to elevated Munc18c tyrosine phosphorylation and dissociation from syntaxin4. At the molecular level, we identify Munc18c Tyr218/219 and Tyr521 as key residues that mediate Munc18c interaction with PTP1B. Further, we uncover an essential role of Munc18c total tyrosine phosphorylation in general, and Tyr218/219 and Tyr521 in particular, in regulating its interactions and glucose uptake in adipocytes.

CONCLUSION

In conclusion, our findings identify PTP1B as the first known tyrosine phosphatase for Munc18c and a regulator of its phosphorylation and function in adipocytes.

背景

蛋白酪氨酸磷酸酶 1B（PTP1B）是胰岛素信号和肥胖的生理调节剂，也是治疗肥胖症和糖尿病的药物靶点。PTP1B 代谢作用的分子机制需要进一步研究。

结果

在此，我们鉴定出 Munc18c 是脂肪细胞和体内的一种新型 PTP1B 底物。我们证明了 Munc18c 在脂肪组织中的营养调节，表明高脂肪喂养时表达降低。此外，PTP1B 缺乏会导致 Munc18c 酪氨酸磷酸化增加，并与突触融合蛋白 4 分离。在分子水平上，我们确定 Munc18c Tyr218/219 和 Tyr521 是介导 Munc18c 与 PTP1B 相互作用的关键残基。此外，我们揭示了 Munc18c 总酪氨酸磷酸化在调节其在脂肪细胞中的相互作用和葡萄糖摄取中的重要作用，特别是 Tyr218/219 和 Tyr521。