biostudies-literatureRusanescu GNIDDK NIH HHSNCI NIH HHS305-14https://www.ebi.ac.uk/biostudies/studies/S-EPMC545812biostudies-literatureUnknown24(2)Calcium influx can promote neuronal differentiation and survival, at least in part by activating Ras and its downstream targets, including the Erk pathway. However, excessive calcium influx can initiate molecular signals leading to neuronal death during excitotoxicity or in neurodegenerative diseases. Here we describe a new signaling pathway associated with calcium influx that contributes to neuronal cell death in cerebellar neurons. Influx of calcium, mediated either by L-type voltage-sensitive calcium channels or glutamate receptors, is associated with the suppression of brain-derived neurotrophic factor (BDNF) activation of Ras and its effectors Erk and Akt. This is the result of enhanced association of the tyrosine phosphatase Shp-2 with TrkB receptors, which inhibits BDNF-induced TrkBThe EMBO journalTyrosine phosphatase SHP-2 is a mediator of activity-dependent neuronal excitotoxicity.PMC545812P30 DK034928DK 50693R01 CA047391CA491452CA47391P30-DK34928R01 DK050693Yang WBai ANeel BGRusanescu GFeig LAfalseTyrosine phosphatase SHP-2 is a mediator of activity-dependent neuronal excitotoxicity.Calcium influx can promote neuronal differentiation and survival, at least in part by activating Ras and its downstream targets, including the Erk pathway. However, excessive calcium influx can initiate molecular signals leading to neuronal death during excitotoxicity or in neurodegenerative diseases. Here we describe a new signaling pathway associated with calcium influx that contributes to neuronal cell death in cerebellar neurons. Influx of calcium, mediated either by L-type voltage-sensitive calcium channels or glutamate receptors, is associated with the suppression of brain-derived neurotrophic factor (BDNF) activation of Ras and its effectors Erk and Akt. This is the result of enhanced association of the tyrosine phosphatase Shp-2 with TrkB receptors, which inhibits BDNF-induced TrkB2005-01-01T00:00:00Z2005 Jan2025-04-20T01:38:27.13Z2019-03-27T01:08:32ZS-EPMC5458121565075010.1038/sj.emboj.7600522