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Feedback regulation of MAPK signalling by an RNA-binding protein

Author

Listed:
  • Reiko Sugiura

    (Kobe University Graduate School of Medicine)

  • Ayako Kita

    (Kobe University Graduate School of Medicine)

  • Yasuhito Shimizu

    (Kobe University Graduate School of Medicine)

  • Hisato Shuntoh

    (Kobe University School of Medicine)

  • Susie O. Sio

    (Kobe University Graduate School of Medicine
    University of the Philippines Manila)

  • Takayoshi Kuno

    (Kobe University Graduate School of Medicine)

Abstract

Mitogen-activated protein kinases (MAPKs) are evolutionarily conserved enzymes that convert extracellular signals into various outputs such as cell growth, differentiation and cell death1,2,3,4. MAPK phosphatases selectively inactivate MAPKs by dephosphorylating critical phosphothreonine and phosphotyrosine residues5,6. The transcriptional induction of MAPK phosphatase expression by various stimuli, including MAPK activation, has been well documented as a negative-feedback mechanism of MAPK signalling7,8. Here we show that Rnc1, a novel K-homology-type RNA-binding protein in fission yeast, binds and stabilizes Pmp1 messenger RNA9, the MAPK phosphatase for Pmk1 (refs 10, 11). Rnc1 therefore acts as a negative regulator of Pmk1 signalling. Notably, Pmk1 phosphorylates Rnc1, causing enhancement of the RNA-binding activity of Rnc1. Thus, Rnc1 is a component of a new negative-feedback loop that regulates the Pmk1 pathway through its binding to Pmp1 mRNA. Our findings—the post-transcriptional mRNA stabilization of a MAPK phosphatase mediated by an RNA-binding protein—provide an additional regulatory mechanism for fine-tuning of MAPK signalling pathways.

Suggested Citation

  • Reiko Sugiura & Ayako Kita & Yasuhito Shimizu & Hisato Shuntoh & Susie O. Sio & Takayoshi Kuno, 2003. "Feedback regulation of MAPK signalling by an RNA-binding protein," Nature, Nature, vol. 424(6951), pages 961-965, August.
    • Handle: RePEc:nat:nature:v:424:y:2003:i:6951:d:10.1038_nature01907
    DOI: 10.1038/nature01907
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