Meta-Biol

• Pathways

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)