PathwayStep5219 PathwayStep5225 Prolonged ERK activation events After NGF binding, activated Trk receptors provide multiple docking sites for adaptor proteins and enzymes. Two docking proteins, the Ankyrin-Rich Membrane Spanning protein (ARMS/Kidins220) and Fibroblast growth factor receptor substrate 2 (Frs2), target signaling molecules in response to NGF stimulation and link receptor activation with the MAP kinase (also called the Extracellular signal-Regulated Kinase cascade, ERK) cascade, an essential process for growth factor-induced cell proliferation and differentiation.<br>A feature of NGF signaling is the sustained activation of the MAPK cascade. This is achieved by the small G protein, Rap1 which binds to and activates B-Raf, an activator of the MAPK cascade. Rap1 is a member of the Ras family of G proteins and like all G proteins, Rap1 is in an inactive state when bound to GDP and is active when bound to GTP. A specific GEF (guanine nucleotide exchange factor) called C3G can activate Rap1 by exchanging GDP for GTP. Authored: Nasi, S, Annibali, D, 2006-10-10 09:07:07 Edited: Jassal, B, 2006-10-10 09:20:18 GENE ONTOLOGYGO:0000186 Pubmed12765839 Pubmed9069267 Reactome Database ID Release 43169893 Reactome, http://www.reactome.org ReactomeREACT_12005 Reviewed: Greene, LA, 2007-11-08 15:39:37 Frs2-mediated activation ARMS-mediated activation