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C. elegans SUR-6/PR55 cooperates with LET-92/protein phosphatase 2A and promotes Raf activity independently of inhibitory Akt phosphorylation sites.

Protein phosphatase 2A (PP2A) can both positively and negatively influence the Ras/Raf/MEK/ERK signaling pathway, but its relevant substrates are largely unknown. In C. elegans, the PR55/B regulatory subunit of PP2A, which is encoded by sur-6, positively regulates Ras-mediated vulval induction and acts at a step between Ras and Raf. We show that the catalytic subunit (C) of PP2A, which is encoded by let-92, also positively regulates vulval induction. Therefore SUR-6/PR55 and LET-92/PP2A-C probably act together to dephosphorylate a Ras pathway substrate. PP2A has been proposed to activate the Raf kinase by removing inhibitory phosphates from Ser259 from Raf-1 or from equivalent Akt phosphorylation sites in other Raf family members. However, we find that mutant forms of C. elegans LIN-45 RAF that lack these sites still require sur-6. Therefore, SUR-6 must influence Raf activity via a different mechanism. SUR-6 and KSR (kinase suppressor of Ras) function at a similar step in Raf activation but our genetic analysis suggests that KSR activity is intact in sur-6 mutants. We identify the kinase PAR-1 as a negative regulator of vulval induction and show that it acts in opposition to SUR-6 and KSR-1. In addition to their roles in Ras signaling, SUR-6/PR55 and LET-92/PP2A-C cooperate to control mitotic progression during early embryogenesis.

Pubmed ID: 14724126


  • Kao G
  • Tuck S
  • Baillie D
  • Sundaram MV


Development (Cambridge, England)

Publication Data

February 3, 2004

Associated Grants

  • Agency: NCI NIH HHS, Id: CA87512
  • Agency: NCI NIH HHS, Id: R01 CA087512

Mesh Terms

  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins
  • Drosophila Proteins
  • Female
  • Mitogen-Activated Protein Kinase 1
  • Mutation
  • Phosphoprotein Phosphatases
  • Phosphorylation
  • Protein Phosphatase 2
  • Protein Tyrosine Phosphatases
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins c-raf
  • Vulva