Negative Feedback Phosphorylation of Gγ Subunit Ste18 and the Ste5 Scaffold Synergistically Regulates MAPK Activation in Yeast
| Autor: | Matthew P. Torres, Shilpa Choudhury, Parastoo Baradaran-Mashinchi |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Scaffold protein MAPK/ERK pathway Saccharomyces cerevisiae Proteins 030102 biochemistry & molecular biology MAP Kinase Signaling System Chemistry G protein Protein subunit Saccharomyces cerevisiae Article General Biochemistry Genetics and Molecular Biology Cell biology 03 medical and health sciences 030104 developmental biology lcsh:Biology (General) GTP-Binding Protein gamma Subunits Heterotrimeric G protein Fus3 Point Mutation Phosphorylation lcsh:QH301-705.5 Ste5 Adaptor Proteins Signal Transducing |
| Zdroj: | Cell reports Cell Reports, Vol 23, Iss 5, Pp 1504-1515 (2018) |
| ISSN: | 2211-1247 |
| Popis: | 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. In Brief 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. |
| Databáze: | OpenAIRE |
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