caa a22 4500 606233881 CHVBK 20210128101234.0 cr unu---uuuuu 210128e20150401xx s 000 0 eng 10.1007/s11010-014-2311-0 doi (NATIONALLICENCE)springer-10.1007/s11010-014-2311-0 RC3/neurogranin negatively regulates extracellular signal-regulated kinase pathway through its interaction with Ras [Elektronische Daten] [Kanghyun Ryoo, Sang-gil Hwang, Kwang Kim, Eui-Ju Choi] RC3/neurogranin is a postsynaptic protein and plays pivotal roles in spatial learning and emotional anxiety as well as synaptic plasticity. The expression level of RC3 is dynamically changed during developmental stages, but the function of RC3 in brain development is not well understood yet. Neurotrophins interact with tropomyosin-related kinase receptors to activate Ras-extracellular signal-regulated kinase (ERK) pathway and can also induce neuronal differentiation. In this study, we demonstrate that RC3 inhibits Ras-ERK pathway by interaction with Ras and controls neurite outgrowth induced by neurotrophins. In PC12 cells, RC3 inhibits nerve growth factor (NGF)-induced activation of Ras and thereby ERK1/2 signaling cascade as well as neurite outgrowth induced by NGF. We found Ras is the target of the inhibitory function of RC3, because RC3 interacts with Ras and suppresses the elevated affinity of Ras to Ras-binding domain of Raf-1. Meanwhile, already activated Raf-1 by Ras activity is not affected by RC3. Furthermore, depletion of RC3 by RNA interference drastically enhances the stimulation of ERK1/2 and neurite outgrowth induced by brain-derived neurotrophic factor in hippocampal neurons. These findings suggest that RC3 is a novel natural inhibitor of Ras-ERK1/2 signaling axis, leading to negatively regulate neuronal differentiation induced by neurotrophins. Springer Science+Business Media New York, 2014 RC3 nationallicence Neurotrophin nationallicence Neurite outgrowth nationallicence Ras nationallicence ERK1/2 nationallicence Ryoo Kanghyun Laboratory of Cell Death and Human Disease, Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University, 136-701, Seoul, Republic of Korea aut Hwang Sang-gil Laboratory of Cell Death and Human Disease, Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University, 136-701, Seoul, Republic of Korea aut Kim Kwang Laboratory of Cell Death and Human Disease, Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University, 136-701, Seoul, Republic of Korea aut Choi Eui-Ju Laboratory of Cell Death and Human Disease, Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University, 136-701, Seoul, Republic of Korea aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 402/1-2(2015-04-01), 33-40 0300-8177 402:1-2<33 2015 402 11010 https://doi.org/10.1007/s11010-014-2311-0 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 brief-communication jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-014-2311-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ryoo Kanghyun Laboratory of Cell Death and Human Disease, Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University, 136-701, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Hwang Sang-gil Laboratory of Cell Death and Human Disease, Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University, 136-701, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Kim Kwang Laboratory of Cell Death and Human Disease, Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University, 136-701, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Choi Eui-Ju Laboratory of Cell Death and Human Disease, Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University, 136-701, Seoul, Republic of Korea aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 402/1-2(2015-04-01), 33-40 0300-8177 402:1-2<33 2015 402 11010