ROLE OF STEP, A STRIATAL ENRICHED TYROSINE PHOSPHATASE, IN NEURONAL CELL DEATH

STEP（一种富含纹状体的酪氨酸磷酸酶）在神经细胞死亡中的作用

• 批准号: 7959368
• 负责人: Surojit Paul
• 金额: $ 11.37万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7959368
• 关键词: Cell Line; Cell Nucleus; Chemicals; Computer Retrieval of Information on Scientific Projects Database; Corpus striatum structure; Extracellular Signal Regulated Kinases; Functional disorder; Funding; Glutamates; Grant; Institution; MAP Kinase Signaling Pathways; MAPK14 gene; N-Methyl-D-Aspartate Receptors; Neurons; Nuclear Translocation; Play; Protein Tyrosine Phosphatase; Research; Research Personnel; Resources; Role; Sorbitol; Source; Stress; Testing; Tyrosine Phosphorylation; United States National Institutes of Health; mitogen-activated protein kinase p38; neuron loss; programs; research study

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. Project 4: PI  Surojit Paul SUBPROJECT DESCRIPTION In our initial project we proposed to test the hypothesis that STEP, a striatal enriched tyrosine phosphatase plays a critical role in neuronal cell death by regulating the temporal activity of p38 and ERK MAP kinase signaling pathway. During the previous funding periods we have demonstrated that p38 MAP kinase is a substrate of STEP. Bio-chemical and immunocytochemical experiments in cell lines showed that active STEP can block stress (sorbitol) induced tyrosine phosphorylation and nuclear translocation of p38 MAP kinase. Studies in primary neuronal cultures further established that transient stimulation glutamate/NMDA receptor leads to activation and nuclear translocation of p38 MAP kinase. Whereas a more sustained stimulation of glutamate/NMDA receptor leads to activation of STEP, which limits the duration of p38 activity as well as its translocation to the nucleus.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 项目 4：PI Surojit Paul 子项目描述 在我们最初的项目中，我们提出测试这样的假设：STEP（一种富含纹状体的酪氨酸磷酸酶）通过调节 p38 和 ERK MAP 激酶信号通路的时间活性在神经元细胞死亡中发挥关键作用。在之前的资助期间，我们已经证明 p38 MAP 激酶是 STEP 的底物。细胞系中的生化和免疫细胞化学实验表明，活性 STEP 可以阻断应激（山梨醇）诱导的酪氨酸磷酸化和 p38 MAP 激酶的核转位。原代神经元培养物的研究进一步证实，瞬时刺激谷氨酸/NMDA 受体会导致 p38 MAP 激酶的激活和核转位。而更持续地刺激谷氨酸/NMDA 受体会导致 STEP 激活，从而限制 p38 活性的持续时间及其向细胞核的易位。