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。 项目4：PI  Surojit Paul 子项目说明 在我们最初的项目中，我们提出了一个假设，即STEP，纹状体富集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起着关键作用。在以前的资助期间，我们已经证明了p38 MAP激酶是STEP的底物。在细胞系中的生物化学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。在原代神经元培养物中的研究进一步证实，瞬时刺激谷氨酸/NMDA受体导致p38 MAP激酶的激活和核转位。而谷氨酸/NMDA受体的更持续的刺激导致STEP的激活，这限制了p38活性的持续时间以及其向核的移位。

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.