Protein-tyrosine phosphatases PTP1B and Syp are modulators of insulin-stimulated translocation of GLUT4 in transfected rat adipose cells
Protein-tyrosine phosphatases PTP1B and Syp are modulators of insulin-stimulated translocation of GLUT4 in transfected rat adipose cells
复制标题
DOI：
10.1074/jbc.272.12.8026
复制
发表时间：
1997-03-21
影响因子：
4.8
通讯作者：
Quon, MJ
中科院分区：
文献类型：
--
作者：
Chen, H;Wertheimer, SJ;Quon, MJ
蛋白酪氨酸磷酸酶PTP 1B和Syp都被认为是胰岛素促有丝分裂作用的调节剂，然而，这些蛋白酪氨酸磷酸酶在胰岛素代谢作用中的作用还没有得到很好的表征。我们直接评估了PTP 1B和Syp调节胰岛素刺激的胰岛素转运的能力，在生理学相关的胰岛素靶细胞中的响应性葡萄糖转运蛋白GLUT 4，用野生型PTP 1B（PTP 1B WT）、野生型Syp（Syp-WT）或催化失活突变体PTP 1B-C/S或SypC/S。研究了这些构建体的过表达对共转染的表位标记的GLUT 4的胰岛素刺激的易位的影响，过表达PTP 1B-C/S或Syp-WT的细胞具有与仅表达表位标记的GLUT 4的对照细胞获得的胰岛素剂量-反应曲线相似的胰岛素剂量-反应曲线。对于过表达PTP 1B-WT的细胞，在每个胰岛素剂量下细胞表面上的GLUT 4水平有趣的是，过表达显性抑制性突变体Syp-C/S的细胞也具有小的但统计学上显著的胰岛素响应性损害。在最大刺激浓度的胰岛素（60 nM）下，细胞表面表位标记的GLUT 4比对照细胞的低约20%。Syp和PTP 1B构建体的高水平过表达的作用可能不反映生理条件下发生的情况。然而，我们的数据提高了PTP 1B可能是胰岛素刺激的葡萄糖转运的负调节剂的可能性，而Syp可能作为胰岛素代谢作用的正介体具有小的作用。
The protein-tyrosine phosphatases PTP1B and Syp have both been implicated as modulators of the mitogenic actions of insulin, However, the roles of these protein-tyrosine phosphatases in the metabolic actions of insulin are not well characterized, In this study, we directly assessed the ability of PTP1B and Syp to modulate insulin-stimulated translocation of the insulin-responsive glucose transporter GLUT4 in a physiologically relevant insulin target cell, Primary cultures of rat adipose cells were transiently transfected with either wild-type PTP1B (PTP1B WT), wild-type Syp (Syp-WT), or the catalytically inactive mutants PTP1B-C/S or SypC/S, The effects of overexpression of these constructs on insulin-stimulated translocation of a co-transfected epitope-tagged GLUT4 were studied, Cells overexpressing either PTP1B-C/S or Syp-WT had insulin dose-response curves similar to those obtained with control cells expressing only epitope-tagged GLUT4, In contrast, for cells overexpressing PTP1B-WT the level of GLUT4 on the cell surface at each insulin dose (ranging from 0 to 60 nM) was significantly lower than that observed in the control cells, Interestingly, cells overexpressing the dominant inhibitory mutant Syp-C/S also had a small but statistically significant impairment in insulin responsiveness, At a maximally stimulating concentration of insulin (60 nM), cell surface epitope-tagged GLUT4 was approximately 20% less than that of the control cells, It is possible that effects from high level overexpression of Syp and PTP1B constructs may not reflect what occurs under physiological conditions, Nevertheless, our data raise the possibility that PTP1B may be a negative regulator of insulin-stimulated glucose transport, while Syp may have a small role as a positive mediator of the metabolic actions of insulin.