Rap1-GTP phosphorylates Raf1

Stable Identifier
Reaction [transition]
Rattus norvegicus
SVG |   | PPTX  | SBGN
Rap1-GTP phosphorylates Raf1

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.
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.

Literature References
PubMed ID Title Journal Year
9560161 Rap1 mediates sustained MAP kinase activation induced by nerve growth factor

Stork, PJ, McCleskey, EW, Dillon, T, Eckert, SP, Yao, H, York, RD, Ellig, CL

Nature 1998
Catalyst Activity

protein serine/threonine kinase activity of Rap1-GTP:Raf1 complex [cytosol]

Orthologous Events
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