IDENTIFICATION OF ATM TARGETS BY PROTEOMIC ANALYSIS IN SH-SY5Y NEURON-LIKE CELLS

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。 我们以前的研究结果表明，在分化的人神经元样细胞中，细胞质ATM在激活Akt以响应胰岛素中起直接作用。 我们的研究结果还表明，ATM易位从细胞核到细胞质中分化的人SH-SY 5 Y细胞。 与这些观察结果一致，我们的结果表明KU-55933（ATM的特异性抑制剂）对Akt的抑制发生在分化的SH-SY 5 Y细胞中，但不发生在未分化的细胞（其倾向于更像成纤维细胞而不是神经元样）中。 Akt是PI 3-激酶信号通路的主要组分，并且已被证明参与包括神经元存活在内的多种生理过程。 我们的研究结果表明，从ATM到Akt的信号响应胰岛素和IGF-I可能是ATM和神经元存活之间的直接联系。

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. Our previous results demonstrate that cytoplasmic ATM plays a direct role in activating Akt in response to insulin in differentiated human neuron-like cells. Our results also demonstrate that ATM translocates from nucleus to the cytoplasm in differentiated human SH-SY5Y cells. Agreeing with these observations, our results show that inhibition of Akt by KU-55933, a specific inhibitor of ATM, occurs in differentiated SH-SY5Y cells, but not in undifferentiated cells (which tend to be more fibroblast like vs. neuron-like). Akt is a major component of the PI 3-kinase signaling pathway and has been shown to participate in multiple physiological processes including neuronal survival. Our results suggest that the signaling from ATM to Akt in response to insulin and IGF-I may be a direct link between ATM and neuronal survival.