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The Spatial Organization of Ras Signaling

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Ras Superfamily Small G Proteins: Biology and Mechanisms 1

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Abstract

Ras or “Rat sarcoma” is a central node in signal transduction networks that includes a range of oncogenic proteins in its family. These small guanine nucleotide-binding proteins transmit signals from lipid membranes in the cell with which they interact by an acquired affinity through posttranslational modifications at their C-terminal hypervariable region (HVR). Ras bound to the plasma membrane can be switched to the active, GTP-bound state by guanine nucleotide exchange factors (GEFs) that interact with activated growth factor receptors. Signals are then transmitted by the activation of effector proteins through spatial dimensionality reduction from a 3D cytosolic volume to a 2D plasma membrane surface. The enrichment of Ras at the plasma membrane is therefore an important parameter that determines Ras signaling output. Based on the finding that GTPases of the Ras family use farnesyl-binding chaperones to maintain their spatial organization, we discuss the molecular components and opposed mechanisms of directional flux and diffusional randomization that partition Ras proteins on membranes. The pharmacological modulation of these spatially organizing systems can be exploited to affect oncogenic Ras signaling in cancer cells.

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Authors and Affiliations

  1. Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany

    Björn Papke, Malte Schmick, Nachiket Vartak & Philippe I. H. Bastiaens

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  1. Björn Papke
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  2. Malte Schmick
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  3. Nachiket Vartak
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  4. Philippe I. H. Bastiaens
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Correspondence to Philippe I. H. Bastiaens .

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  1. Max-Planck-Institute of Molecular Physiology, Dortmund, Nordrhein-Westfalen, Germany

    Alfred Wittinghofer

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Papke, B., Schmick, M., Vartak, N., Bastiaens, P.I.H. (2014). The Spatial Organization of Ras Signaling. In: Wittinghofer, A. (eds) Ras Superfamily Small G Proteins: Biology and Mechanisms 1. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1806-1_8

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