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Ras Superfamily Small G Proteins: Biology and Mechanisms 1 pp 99–131Cite as

Posttranslational Modifications of Small G Proteins

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Abstract

The numerous biological functions of Ras superfamily small GTPases are highly dependent upon specific posttranslational modifications that guide their subcellular localization and interaction with regulators and effectors. Canonical modifications of their carboxyl termini include prenylation by farnesyl or geranylgeranyl isoprenoid lipids (Ras, Rho, Rab families). These serve as important components of their membrane targeting motifs and promote membrane binding, analogously to the cotranslational amino-terminal myristoylation of Arf family proteins. Reversible carboxymethylation of the prenylated cysteines and reversible acylation by one or more nearby palmitates promote dynamic membrane interactions to complement the permanent lipid modifications. Small GTPases are also regulated in both normal and disease states by several dynamic non-lipid posttranslational modifications. For example, many Ras and Rho family members are phosphorylated in an isoform-specific manner, largely by a select group of serine/threonine kinases such as protein kinase Cα or protein kinase A. Such phosphorylation events, as well as other modifications such as nitrosylation, mono- and di-ubiquitination, peptidyl-prolyl isomerization, acetylation, and oxidation, typically alter small GTPase location and/or interaction with regulatory molecules. By contrast, several distinct E3 ligases posttranslationally regulate small GTPase abundance and function at distinct cellular sites by promoting polyubiquitination and subsequent proteasomal degradation. Finally, numerous pathogenic bacterial toxins disrupt or enhance small GTPase function by a wide variety of posttranslational modifications including ADP ribosylation for which the Arf proteins are named. Here we summarize the rapidly evolving understanding of this fascinating area of small G protein regulation.

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Authors and Affiliations

  1. Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7295, USA

    Bingying Zhou

  2. Departments of Radiation Oncology and Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7295, USA

    Adrienne D. Cox

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

    Alfred Wittinghofer

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Zhou, B., Cox, A.D. (2014). Posttranslational Modifications of Small G Proteins. 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_5

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