Activated MAPK phosphorylates RAF1

Stable Identifier
R-HSA-5675194
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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RAF1 is phosphorylated by activated MAPK at 6 serine residues (S29, S43, S289, S296, S301 and S642). MAPK-dependent hyperphosphorylation of RAF1 abrogates the ability of activated RAF1 to interact with RAS and is coincident with inactivation of RAF1. RAF1 proteins containing mutation of these phosphorylation sites persist at the plasma membrane, show sustained S338 phosphorylation and persistent activation relative to WT RAF1 protein. In wild type cells, PP2A and the prolyl-isomerase PIN1 contribute to the dephosphorylation of hyperphosphorylated RAF1, allowing subsequent cycles of activation to occur (Dougherty et al, 2005; reviewed in Roskoski, 2010)

Literature References
PubMed ID Title Journal Year
20674547 RAF protein-serine/threonine kinases: structure and regulation

Roskoski, R Jr

Biochem. Biophys. Res. Commun. 2010
15664191 Regulation of Raf-1 by direct feedback phosphorylation

Dougherty, MK, Müller, J, Ritt, DA, Zhou, M, Zhou, XZ, Copeland, TD, Conrads, TP, Veenstra, TD, Lu, KP, Morrison, DK

Mol. Cell 2005
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
protein serine/threonine kinase activity of p-T,Y MAPK monomers and dimers [cytosol]
Physical Entity
Activity
Orthologous Events
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Reviewed
Created