Active TrkA:Phospho-ARMS:Crk:C3G:Rap1-GTP complex B-Raf complex Active TrkA:Phospho-ARMS:Crk:C3G:Rap1:Phospho-B-Raf complex (ARMS)Rap1-GTP binds and activates B-Raf Authored: Nasi, S, Annibali, D, 2006-10-10 09:07:07 Edited: Jassal, B, 2006-10-10 09:20:18 Rap1 binds to B-RAF; as a consequence, B-RAF is recruited to endosomes. The binding event of Rap1 to B-RAF is thought to be very similar to the binding of RAS to RAF-1. In neuronal cells that express B-Raf, NGF induced activation of Rap1 promotes a sustained activation of ERKs and is required for the induction of electrical excitability and a subset of neuron-specific genes. As regards morphological differentiation (e. g. neurite outgrowth in PC12 cells), things are more complex. The transient activation of ERKs via RAS is not sufficient for neurite outgrowth in the absence of additional signals. On the contrary, constitutive activation of Rap1 is sufficient to trigger neurite outgrowth, but it is not necessary for this response.<br>Clearly, morphological differentiation of PC12 cells involves the activation of multiple pathways by NGF. Rap1 activates B-Raf, but inhibits RAF-1. Consequently, Rap1 could have two opposing functions: to limit ERK activation in B-RAF-negative cells and to increase ERK activation in B-Raf-positive cells. Reactome Database ID Release 43169901 Reactome, http://www.reactome.org ReactomeREACT_12046 Reviewed: Greene, LA, 2007-11-08 15:39:37