Protein phosphatases 1 and 2A promote Raf-1 activation by regulating 14-3-3 interactions

@article{Jaumot2001ProteinP1,
  title={Protein phosphatases 1 and 2A promote Raf-1 activation by regulating 14-3-3 interactions},
  author={Montserrat Jaumot and John F. Hancock},
  journal={Oncogene},
  year={2001},
  volume={20},
  pages={3949-3958}
}
Raf-1 activation is a complex process which involves plasma membrane recruitment, phosphorylation, protein-protein and lipid-protein interactions. We now show that PP1 and PP2A serine-threonine phosphatases also have a positive role in Ras dependent Raf-1 activation. General serine-threonine phosphatase inhibitors such sodium fluoride, or ß-glycerophosphate and sodium pyrophosphate, or specific PP1 and PP2A inhibitors including microcystin-LR, protein phosphatase 2A inhibitor I1 or protein… 
The C-terminus of Raf-1 acts as a 14-3-3-dependent activation switch.
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Protein Kinase A Blocks Raf-1 Activity by Stimulating 14-3-3 Binding and Blocking Raf-1 Interaction with Ras*
TLDR
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Dephosphorylation of Ser-259 Regulates Raf-1 Membrane Association*
TLDR
The data show that Ser-259 dephosphorylation contributes to Raf-1 activation by supporting its membrane accumulation rather than by increasing the specific activity of the kinase and provide a mechanistic basis for the support of kinase activation by Raf- 1-associated protein phosphatase 2A.
Regulation of the Raf–MEK–ERK pathway by protein phosphatase 5
TLDR
Protein phosphatase 5 (PP5) was identified as an inactivator that associates with Raf-1 on growth factor stimulation and selectively dephosphorylates an essential activating site, Ser 338, and the results suggest that PP5 is a physiological regulator of Raf- 1 signalling pathways.
14-3-3 Antagonizes Ras-Mediated Raf-1 Recruitment to the Plasma Membrane To Maintain Signaling Fidelity
TLDR
It is shown that 14-3-3 binding, rather than Raf-1 phosphorylation, is required for the correct regulation of kinase activity, and stable association of Raf- 1 with the plasma membrane requires Ras-mediated displacement of 14- 3-3 from CR2.
Positive Regulation of Raf1-MEK1/2-ERK1/2 Signaling by Protein Serine/Threonine Phosphatase 2A Holoenzymes*
TLDR
Findings indicate that PP2A ABαC and ABδC holoenzymes function as positive regulators of Raf1-MEK1/2-ERK2/2 signaling by targeting Raf1 and catalyze dephosphorylation of inhibitory phospho-Ser-259.
Identification of novel in vivo Raf-1 phosphorylation sites mediating positive feedback Raf-1 regulation by extracellular signal-regulated kinase.
TLDR
This study describes the identification of new in vivo Raf-1 phosphorylation sites targeted by ERK and provides a novel mechanism for a positive feedback Raf-2 regulation, and its phosphopeptide composition is similar to that of the general Raf- 1 population.
C. elegans SUR-6/PR55 cooperates with LET-92/protein phosphatase 2A and promotes Raf activity independently of inhibitory Akt phosphorylation sites
TLDR
It is shown that the catalytic subunit (C) of PP2A, which is encoded by let-92, also positively regulates vulval induction, and that SUR-6/PR55 and LET-92/PP2A-C probably act together to dephosphorylate a Ras pathway substrate.
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TLDR
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