Cited by 325Protein Kinase Regulation and GTPase SignalingCellular transport and secretionSphingolipid Metabolism and Signaling

The GDI-like solubilizing factor PDEδ sustains the spatial organization and signalling of Ras family proteins

Chandra, Anchal, Grecco, Hernán E., Pisupati, Venkat, Perera, David, Cassidy, Liam, Skoulidis, Ferdinandos, Ismail, Shehab A., Hedberg, Christian +4 more·2012·Nature Cell Biology

Abstract

We identify a role for the GDI-like solubilizing factor (GSF) PDEδ in modulating signalling through Ras family G proteins by sustaining their dynamic distribution in cellular membranes. We show that the GDI-like pocket of PDEδ binds and solubilizes farnesylated Ras proteins, thereby enhancing their diffusion in the cytoplasm. This mechanism allows more effective trapping of depalmitoylated Ras proteins at the Golgi and polycationic Ras proteins at the plasma membrane to counter the entropic tendency to distribute these proteins over all intracellular membranes. Thus, PDEδ activity augments K/Hras signalling by enriching Ras at the plasma membrane; conversely, PDEδ down-modulation randomizes Ras distributions to all membranes in the cell and suppresses regulated signalling through wild-type Ras and also constitutive oncogenic Ras signalling in cancer cells. Our findings link the activity of PDEδ in determining Ras protein topography to Ras-dependent signalling.

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Crossref · 10.1038/ncb2394

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Authors
Chandra, A., Grecco, H. E., Pisupati, V., Perera, D., Cassidy, L., Skoulidis, F., Ismail, S. A., Hedberg, C., Hanzal-Bayer, M., Venkitaraman, A. R., Wittinghofer, A., & Bastiaens, P. I. H.
Affiliations
  • Max Planck Institute of Molecular Physiology (DE)
  • MRC Cancer Unit (GB)
  • TU Dortmund University (DE)
Corresponding author
Bastiaens, Philippe I. H.
Venue
Nature Cell Biology
Published
2011-12-18
Volume
14
Issue
2
Pages
148-158
ISSN
  • 1465-7392 (ISSN-L)
  • 1476-4679
OpenAlex
W2069537707
Cited by
325
References
63
Citations by year
2026: 14 · 2025: 8 · 2024: 18 · 2023: 18 · 2022: 18 · 2021: 35 · 2020: 26 · 2019: 23 · 2018: 24 · 2017: 35 · 2016: 25 · 2015: 16 · 2014: 28 · 2013: 21 · 2012: 14
FWCI
8.32
Type
journal article
Language
en
Update notices
erratum (2012-02-29)
Open access
closed
Locations
  • Nature Cell Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Max Planck Institute for Plasma Physics (submittedVersion)
  • ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Funders
National Institute for Health and Care Research (CL-2008-14-003)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
Keywords
PDEδ, Ras family GTPases, membrane protein distribution, Golgi apparatus, plasma membrane, Ras signaling, oncogenic Ras, subcellular localization, protein diffusion
MeSH terms
Amino Acid Sequence, Animals, Cell Line, Cell Membrane, Golgi Apparatus, Humans, Intracellular Membranes, Molecular Sequence Data, Protein Binding, Blotting, Western, Signal Transduction, Microscopy, Confocal, ras Proteins, GTP-Binding Proteins, Guanine Nucleotide Dissociation Inhibitors, Fluorescence Resonance Energy Transfer, RNA Interference, Fluorescence Recovery After Photobleaching, Green Fluorescent Proteins, Cyclic Nucleotide Phosphodiesterases, Type 6, Prenylation, Lipoylation, Hep G2 Cells

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