TY - JOUR
T1 - G protein subunit phosphorylation as a regulatory mechanism in heterotrimeric G protein signaling in mammals, yeast, and plants
AU - Chakravorty, David
AU - Assmann, Sarah M.
PY - 2018/11/9
Y1 - 2018/11/9
N2 - 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.
AB - 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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U2 - 10.1042/BCJ20160819
DO - 10.1042/BCJ20160819
M3 - Review article
C2 - 30413679
AN - SCOPUS:85056420875
VL - 475
SP - 3331
EP - 3357
JO - Biochemical Journal
JF - Biochemical Journal
SN - 0264-6021
IS - 21
ER -