Reactome | Activated MAPK phosphorylates RAF1

Activated MAPK phosphorylates RAF1

Stable Identifier

R-HSA-5675194

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

Locations in the PathwayBrowser

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Signal Transduction (Homo sapiens)

- MAPK family signaling cascades (Homo sapiens)
  - MAPK1/MAPK3 signaling (Homo sapiens)
    - RAF/MAP kinase cascade (Homo sapiens)
      - Negative regulation of MAPK pathway (Homo sapiens)
        
        Negative feedback regulation of MAPK pathway (Homo sapiens)
        
        Activated MAPK phosphorylates RAF1 (Homo sapiens)

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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
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
20674547	RAF protein-serine/threonine kinases: structure and regulation Roskoski, R Jr	Biochem. Biophys. Res. Commun.	2010