O-GLCNAC MODIFICATION OF SIGNALING EFFECTORS IN 3T3-L1 NORMAL VS INSULIN

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 在高血糖诱导的胰岛素抵抗的许多模型中，已经证实了胰岛素刺激的Akt活化水平的信号传导缺陷。O-GlcNAc水平的增加与胰岛素信号传导缺陷有因果关系，但介导这些负面影响的特定蛋白质和修饰位点尚不清楚。PI 3-激酶位于Akt活化的上游。潜在地，在胰岛素抵抗状态下参与该途径的分子上的O-GlcNAc增加影响胰岛素信号。将检查正常与胰岛素抵抗状态下参与该途径的分子（例如Akt和PDK 1）的O-GlcNAc修饰状态。如果发现特定蛋白质被修饰，将使用UCSF质谱设施新开发的技术（BEMAD）进行位点定位分析。最终，将在胰岛素信号传导的背景下测试映射的位点的调节功能。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In many models of hyperglycemia induced insulin resistance, a signaling defect at the level of insulin stimulated Akt activation has been demonstrated. Increased levels of O-GlcNAc have been causally linked to insulin signaling defects, but the specific proteins and sites of modification mediating these negative effects are not known. PI 3-kinase is upstream of Akt activation. Potentially, increased O-GlcNAc in the insulin resistant state on molecules involved in this pathway influence insulin signals. The O-GlcNAc modification state of molecules involved in this pathway (e.g. Akt, and PDK1) in normal vs. insulin resistant states will be examined. If specific proteins are found to be modified, site mapping analysis will be performed using a technique (BEMAD) newly developed at the UCSF mass spec facility. Ultimately, mapped sites will be tested for regulatory functions in the context of insulin signaling.