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

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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.