CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling

Ca2+ influx through the NMDA receptor activates RAS guanyl nucleotide exchange factor RasGRF, which promotes formation of active RAS:GTP complexes. CaMKII, also activated by NMDA receptor-mediated Ca2+ influx, can contribute to activation of RAS/RAF/MAPK signaling by phosphorylation of RAF1. ERKs (MAPK1 and MAPK3), activated downstream of RAS signaling, phosphorylate ribosomal protein S6 kinases (RSKs), initiating activation of RSKs (reviewed by Anjum and Blenis 2012). Activated RSKs phosphorylate the transcription factor CREB1 at serine residue S133, thus stimulating CREB1-mediated transcription (De Cesare et al. 1998, Harum et al. 2001, Schinelli et al. 2001, Song et al. 2003).

Summary from Reactome (R-HSA-442742), read 2026-09-23.