Imported:YPM/Sst2

Category:Species - Yeast Pheromone Response Model Back to main model page

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About Sst2

• Sst2 has an N-terminal DEP domain which binds to both the unphosphorylated CTD of Ste2 and to Gpa1. This localizes Sst2 near Gpa1 to exert its RGS function on newly activated Gpa1 in efficient negative feedback. Dixit et al 2014 PMCID: PMC4142594

• Cytoplasmic Sst2 (not bound to Ste2) suppresses basal activation of Gpa1. Dixit et al 2014 PMCID: PMC4142594

• After pathway activation, Sst2 acts to suppress intra-cellular variability (noise). Dixit et al 2014 PMCID: PMC4142594

• Sst2 binds to Ste2 via residue Q304 of Sst2. Mutation Q304N abolishes this interaction; resulting cells have 10-fold lower EC50 than WT and moderately increased maximal activation. Dixit et al 2014 PMCID: PMC4142594

• The binding of Sst2 to Ste2 occurs at unphosphorylated phosphorylation sites on the Ste2 CTD. This interaction competes with phosphorylation and slows Ste2 internalization. Venkapurapu et al 2015

• Overexpression of Sst2 both increases maximal activation and increases EC50. These effects are orthogonal to GPCR expression level. Sridharan et al 2016.

• Mutation of the RGS domain decreases EC50 10-fold and vertically shifts the dose response curve, increasing both basal and maximal activity. This effect is identical to mutating the DEP domain, but the mutations are additive with double-mutants and Sst2 knockouts having 100-fold lower EC50 than WT and vertically shifted dose response curves. Dixit et al 2014 PMCID: PMC4142594

• N terminal 300 residues show homology to segments in two mammalian GTPase-activating proteins (GAPs). The segments have been shown to be necessary and sufficient for GAP activity. Dohlman et al. 1996 PMID 8756677

• Sst2-Myc is found throughout the cytosol, but it not found in the vacuole or nucleus (determined by confocal microscopy). Dohlman et al. 1996 PMID 8756677

• C terminal RGS(Regulator of G protein Signaling)-like domain is also necesary for Sst2 activity in vivo. Dohlman et al. 1996 PMID 8756677

• Sst2 is largely membrane associated. Dohlman et al. 1996 PMID 8756677

• Sst2 stands for SuperSensiTivity to pheromone. Apanovitch et al. 1998 PMID 9537998

• Sst2 acts as a GAP for Gpa1 by stabilizing the transition state of the GTP hydrolysis reaction. Apanovitch et al. PMID 9537998

• Sst2 association with membrane appears to be mainly electrostatic. Dohlman et al. 1996 PMID 8756677

• Sst2 is phosphorylated at S539 by Fus3 in response to pheromone. This slows its degradation without affecting pheromone transcriptional dose response. Garrison et al. 1999 PMID 10593933

• Quantitative Western blots were used to show that there are ~2000 Sst2 molecules per cell prior to pheromone stimulation, and a peak of ~5000 Sst2 molecules per cell about 1 hour after pheromone stimulation. Hao et al. 2003 PMID 12968019

• Sst2 deletion results in 100-fold increase in pheromone sensitivity, but no increase in maximum gene expression. Hao et al. 2003 PMID 12968019

Reactions

RGS(Sst2)/Galpha(Gpa1)/Receptor(Ste2) interactions
G protein nucleotide hydrolysis/exchange
Sst2 synthesis/degradation
Ste12 mediated protein synthesis
Non-specific dephosphorylation
Protein dilution/synthesis due to cell growth

Species Representation

Molecule Type

<modelMoleculeType>Sst2(Ste2_site, MAPK_site, S539~none~PO4)</modelMoleculeType>

Model Seed

<modelSeedSpecies>Sst2(Ste2_site, MAPK_site, S539~none) Sst2_tot_conc</modelSeedSpecies>