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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 项目4：Pi Surojit Paul 子项目描述 在我们最初的项目中，我们提出了验证这一假设的假设，即纹状体富含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，我们已经证明了p38蛋白激酶是STEP的底物。细胞生化和免疫细胞化学实验表明，活性步骤可阻断应激(山梨醇)诱导的酪氨酸磷酸化和p38MAPK的核转位。在原代神经元培养中的研究进一步证实，瞬时刺激谷氨酸/NMDA受体导致p38MAPK的激活和核转位。而对谷氨酸/NMDA受体更持久的刺激导致STEP的激活，从而限制了p38活性的持续时间及其向核内的移位。

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.