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Snf1/AMP-activated protein kinase activates Arf3p to promote invasive yeast growth via a non-canonical GEF domain

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  • Jia-Wei Hsu

    (Institute of Molecular Medicine, College of Medicine, National Taiwan University)

  • Kuan-Jung Chen

    (Institute of Molecular Medicine, College of Medicine, National Taiwan University)

  • Fang-Jen S. Lee

    (Institute of Molecular Medicine, College of Medicine, National Taiwan University
    National Taiwan University Hospital)

Abstract

Active GTP-bound Arf GTPases promote eukaryotic cell membrane trafficking and cytoskeletal remodelling. Arf activation is accelerated by guanine nucleotide-exchange factors (GEFs) using the critical catalytic glutamate in all known Sec7 domain sequences. Yeast Arf3p, a homologue of mammalian Arf6, is required for yeast invasive responses to glucose depletion. Here we identify Snf1p as a GEF that activates Arf3p when energy is limited. SNF1 is the yeast homologue of AMP-activated protein kinase (AMPK), which is a key regulator of cellular energy homeostasis. As activation of Arf3p does not depend on the Snf1p kinase domain, assay of regulatory domain fragments yield evidence that the C-terminal hydrophobic α-helix core of Snf1p is a non-canonical GEF for Arf3p activation. Thus, our study reveals a novel mechanism for regulating cellular responses to energy deprivation, in particular invasive cell growth, through direct Arf activation by Snf1/AMPK.

Suggested Citation

  • Jia-Wei Hsu & Kuan-Jung Chen & Fang-Jen S. Lee, 2015. "Snf1/AMP-activated protein kinase activates Arf3p to promote invasive yeast growth via a non-canonical GEF domain," Nature Communications, Nature, vol. 6(1), pages 1-8, November.
  • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8840
    DOI: 10.1038/ncomms8840
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