Negative Feedback Phosphorylation of Gγ Subunit Ste18 and the Ste5 Scaffold Synergistically Regulates MAPK Activation in Yeast
Summary: Heterotrimeric G proteins (Gαβγ) are essential transducers in G protein signaling systems in all eukaryotes. In yeast, G protein signaling differentially activates mitogen-activated protein kinases (MAPKs)—Fus3 and Kss1—a phenomenon controlled by plasma membrane (PM) association of the scaf...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-05-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718305230 |
| _version_ | 1818309124048289792 |
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| author | Shilpa Choudhury Parastoo Baradaran-Mashinchi Matthew P. Torres |
| author_facet | Shilpa Choudhury Parastoo Baradaran-Mashinchi Matthew P. Torres |
| author_sort | Shilpa Choudhury |
| collection | DOAJ |
| description | Summary: Heterotrimeric G proteins (Gαβγ) are essential transducers in G protein signaling systems in all eukaryotes. In yeast, G protein signaling differentially activates mitogen-activated protein kinases (MAPKs)—Fus3 and Kss1—a phenomenon controlled by plasma membrane (PM) association of the scaffold protein Ste5. Here, we show that phosphorylation of the yeast Gγ subunit (Ste18), together with Fus3 docking on Ste5, controls the rate and stability of Ste5/PM association. Disruption of either element alone by point mutation has mild but reciprocal effects on MAPK activation. Disabling both elements results in ultra-fast and stable bulk Ste5/PM localization and Fus3 activation that is 6 times faster and 4 times more amplified compared to wild-type cells. These results further resolve the mechanism by which MAPK negative feedback phosphorylation controls pathway activation and provides compelling evidence that Gγ subunits can serve as intrinsic regulators of G protein signaling. : Choudhury et al. show that Gγ subunits, besides acting as anchors for their obligate Gβ subunits, have more complex roles in regulating G protein signaling. Furthermore, they show that this tuning of G protein signaling by the phosphorylated Gγ N-terminal tail is achieved by altering the interaction between Gβγ and downstream effectors in a PTM-dependent manner. Keywords: G protein, Ste18, Ste5, phosphorylation, MAPK, synergistic, signaling, G protein γ, subunit, scaffold, feedback |
| first_indexed | 2024-12-13T07:25:10Z |
| format | Article |
| id | doaj.art-d473f429fdad4e96a15ebd52faf2b949 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-13T07:25:10Z |
| publishDate | 2018-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-d473f429fdad4e96a15ebd52faf2b9492022-12-21T23:55:19ZengElsevierCell Reports2211-12472018-05-0123515041515Negative Feedback Phosphorylation of Gγ Subunit Ste18 and the Ste5 Scaffold Synergistically Regulates MAPK Activation in YeastShilpa Choudhury0Parastoo Baradaran-Mashinchi1Matthew P. Torres2School of Biological Sciences, Georgia Institute of Technology, 950 Atlantic Drive, Atlanta, GA 30332, USASchool of Biological Sciences, Georgia Institute of Technology, 950 Atlantic Drive, Atlanta, GA 30332, USASchool of Biological Sciences, Georgia Institute of Technology, 950 Atlantic Drive, Atlanta, GA 30332, USA; Corresponding authorSummary: Heterotrimeric G proteins (Gαβγ) are essential transducers in G protein signaling systems in all eukaryotes. In yeast, G protein signaling differentially activates mitogen-activated protein kinases (MAPKs)—Fus3 and Kss1—a phenomenon controlled by plasma membrane (PM) association of the scaffold protein Ste5. Here, we show that phosphorylation of the yeast Gγ subunit (Ste18), together with Fus3 docking on Ste5, controls the rate and stability of Ste5/PM association. Disruption of either element alone by point mutation has mild but reciprocal effects on MAPK activation. Disabling both elements results in ultra-fast and stable bulk Ste5/PM localization and Fus3 activation that is 6 times faster and 4 times more amplified compared to wild-type cells. These results further resolve the mechanism by which MAPK negative feedback phosphorylation controls pathway activation and provides compelling evidence that Gγ subunits can serve as intrinsic regulators of G protein signaling. : Choudhury et al. show that Gγ subunits, besides acting as anchors for their obligate Gβ subunits, have more complex roles in regulating G protein signaling. Furthermore, they show that this tuning of G protein signaling by the phosphorylated Gγ N-terminal tail is achieved by altering the interaction between Gβγ and downstream effectors in a PTM-dependent manner. Keywords: G protein, Ste18, Ste5, phosphorylation, MAPK, synergistic, signaling, G protein γ, subunit, scaffold, feedbackhttp://www.sciencedirect.com/science/article/pii/S2211124718305230 |
| spellingShingle | Shilpa Choudhury Parastoo Baradaran-Mashinchi Matthew P. Torres Negative Feedback Phosphorylation of Gγ Subunit Ste18 and the Ste5 Scaffold Synergistically Regulates MAPK Activation in Yeast Cell Reports |
| title | Negative Feedback Phosphorylation of Gγ Subunit Ste18 and the Ste5 Scaffold Synergistically Regulates MAPK Activation in Yeast |
| title_full | Negative Feedback Phosphorylation of Gγ Subunit Ste18 and the Ste5 Scaffold Synergistically Regulates MAPK Activation in Yeast |
| title_fullStr | Negative Feedback Phosphorylation of Gγ Subunit Ste18 and the Ste5 Scaffold Synergistically Regulates MAPK Activation in Yeast |
| title_full_unstemmed | Negative Feedback Phosphorylation of Gγ Subunit Ste18 and the Ste5 Scaffold Synergistically Regulates MAPK Activation in Yeast |
| title_short | Negative Feedback Phosphorylation of Gγ Subunit Ste18 and the Ste5 Scaffold Synergistically Regulates MAPK Activation in Yeast |
| title_sort | negative feedback phosphorylation of gγ subunit ste18 and the ste5 scaffold synergistically regulates mapk activation in yeast |
| url | http://www.sciencedirect.com/science/article/pii/S2211124718305230 |
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