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: 7720122
• 负责人: Surojit Paul
• 金额: $ 28.25万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7720122
• 关键词: Cell Line; Cell Nucleus; Chemicals; Computer Retrieval of Information on Scientific Projects Database; Corpus striatum structure; Extracellular Signal Regulated Kinases; 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; human MAPK14 protein; mitogen-activated protein kinase p38; neuron loss; 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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 项目4：PI Surojit Paul 子标记描述 在我们的最初项目中，我们提出的是测试以下假设：沿纹状体富集的酪氨酸磷酸酶通过调节p38和ERK MAP MAP激酶信号通路的时间活性，在神经元细胞死亡中起关键作用。在前面的资金期间，我们已经证明了p38 MAP激酶是步骤的底物。细胞系中的生物化学和免疫细胞化学实验表明，活性步骤可以阻止应激（山梨糖醇）诱导的酪氨酸磷酸化和p38 MAP激酶的核转运。一级神经元培养的研究进一步确定，瞬时刺激谷氨酸/NMDA受体会导致p38 MAP激酶的激活和核易位。而对谷氨酸/NMDA受体的持续刺激会导致步骤激活，这限制了p38活性的持续时间以及其转移到核的持续时间。