Heterotrimeric G proteins composed of Gα, Gβ, and Gγ subunits are vital eukaryotic signaling elements that convey information from ligand-regulated G protein-coupled receptors (GPCRs) to cellular effectors. Heterotrimeric G protein-based signaling pathways are fundamental to human health [Biochimica et Biophysica Acta (2007) 1768, 994–1005] and are the target of >30% of pharmaceuticals in clinical use [Biotechnology Advances (2013) 31, 1676–1694; Nature Reviews Drug Discovery (2017) 16, 829–842]. This review focuses on phosphorylation of G protein subunits as a regulatory mechanism in mammals, budding yeast, and plants. This is a re-emerging field, as evidence for phosphoregulation of mammalian G protein subunits from biochemical studies in the early 1990s can now be complemented with contemporary phosphoproteomics and genetic approaches applied to a diversity of model systems. In addition, new evidence implicates a family of plant kinases, the receptor-like kinases, which are monophyletic with the interleukin-1 receptor-associated kinase/Pelle kinases of metazoans, as possible GPCRs that signal via subunit phosphorylation. We describe early and modern observations on G protein subunit phosphorylation and its functional consequences in these three classes of organisms, and suggest future research directions.
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Cover Image
Cover Image
The cover image shows an artistic representation of the fluorescence-based assay of deadenylase activity used by Pavanello et al. in this issue, with fluorescence proportional to enzyme activity. Fluorescence (λem = 528 nm) was detected in a multi-mode reader using 96-well plates. Activity of different enzyme complexes (left to right) was measured at various time points (top to bottom). Controls (inactive enzyme preparations and no enzyme controls) were also included (bottom two rows). Pavanello et al. report that the central region of CNOT1 and CNOT9 stimulates deadenylation by the Ccr4–Not nuclease module (see pages 3437–3450).
G protein subunit phosphorylation as a regulatory mechanism in heterotrimeric G protein signaling in mammals, yeast, and plants
David Chakravorty, Sarah M. Assmann; G protein subunit phosphorylation as a regulatory mechanism in heterotrimeric G protein signaling in mammals, yeast, and plants. Biochem J 15 November 2018; 475 (21): 3331–3357. doi: https://doi.org/10.1042/BCJ20160819
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