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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
Department of Genetics, University of Pennsylvania, Philadelphia, USA.
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Pathogenesis (UCMP) (Faculty of Medicine).
Department of Biological Sciences, Simon Fraser University, Canada.
Department of Genetics, University of Pennsylvania, Philadelphia, USA.
2004 (English)In: Development, ISSN 0950-1991, E-ISSN 1477-9129, Vol. 131, no 4, 755-765 p.Article in journal (Refereed) Published
Abstract [en]

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 ofC. 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.

Place, publisher, year, edition, pages
Cambridge: Company of Biologists Limited , 2004. Vol. 131, no 4, 755-765 p.
Keyword [en]
Animals, Animals; Genetically Modified, Caenorhabditis elegans/embryology/*enzymology/genetics, Caenorhabditis elegans Proteins/metabolism, Drosophila Proteins, Female, Mutation, Phosphoprotein Phosphatase/genetics/*metabolism, Phosphorylation, Protein-Serine-Threonine Kinases/metabolism, Protein-Tyrosine-Phosphatase/metabolism, Proto-Oncogene Proteins/*metabolism, Proto-Oncogene Proteins c-akt, Proto-Oncogene Proteins c-raf/*metabolism, Vulva/embryology
URN: urn:nbn:se:umu:diva-17951DOI: 10.1242/dev.00987PubMedID: 14724126OAI: diva2:157624
Available from: 2007-11-23 Created: 2007-11-23 Last updated: 2011-04-01Bibliographically approved

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Kao, GautamTuck, Simon
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