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[[Category:Reactions - Yeast Pheromone Response Model]]
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==[[Ste12]] mediated protein synthesis==

*[[Dig2]], [[Far1]], [[Fus3]], [[Gpa1]], [[Msg5]], [[Ptp2]], [[Sst2]], [[Ste2]] and [[Ste12]] expression is upregulated in response to [[pheromone]] (in addition to expression of other proteins not included in this model).  Roberts et al. 2000 PMID 10657304

*[[Ste3]] expression is rapidly upregulated in response to treatment with a-factor.  Hagen and Sprague. 1984 PMID 6436496

*Activity of pheromone-responsive reporter gene (8 tandem copies of PRE driving lacZ) in absence of pheromone is altered by pathway mutations.  Hasson et al. 1994 PMID 8289786
**down about 10-fold when ste4, ste18, or ste5 is mutated
**down about 100-fold when ste7, ste11, or ste12 is mutated
**up about 3-fold when ste2 is mutated

===Reaction Definition===
When [[Ste12 mediated protein synthesis]] is included in a model, the synthesis rates of several proteins specified on elsewhere in the wiki must be decreased such that the steady-state abundance of each protein is properly maintained.  Basal activation of [[Ste12]] (in the absence of pheromone) will result in some additional level of synthesis of the proteins listed below, and so the synthesis rates of these proteins must be decreased elsewhere commensurately.  See [[Protein dilution/synthesis due to cell growth]] for synthesis of [[Dig2]], [[Far1]], [[Fus3]], [[Msg5]], [[Ptp]], and [[Ste12]].  See [[Gpa1 synthesis/degradation]], [[Sst2 synthesis/degradation]] and [[Ste2 synthesis/endocytosis/degradation]] for synthesis of [[Gpa1]], [[Sst2]] and [[Ste2]].

As detailed on the [[Dig1/Dig2/Ste12_phosphorylation#Ste12_Phosphorylation|Ste12 phosphorylation page]], we are assuming that [[Ste12]] does not need to be phosphorylates by [[Fus3]] or [[Kss1]] to be active, and that being free from [[Dig1]] and [[Dig2]] is sufficient for [[Ste12]] to initiate gene expression.

Rather than model the details of transcription and translation, we shall approximate the process with saturation kinetics of the form Ste12 -> Ste12 + protein, occuring at a rate of kcat*Ste12/(Km+Ste12).  The [[BioNetGen]] expression that defines this rate law is ''Sat(kcat,Km)''.

<modelRxnFull><modelRxnRule>
 Ste12(Dig1_site, Dig2_site, MAPK_site) -> 
 Ste12(Dig1_site, Dig2_site, MAPK_site) + Dig2(Ste12_site, MAPK_site, PO4_site~none)
</modelRxnRule>
*This reaction occurs at a rate that is specified by <modelRxnParam>Sat([[ksynth_Ste12_Dig2]],[[Km_synth_Ste12_Dig2]])</modelRxnParam></modelRxnFull>

<modelRxnFull><modelRxnRule>
 Ste12(Dig1_site, Dig2_site, MAPK_site) -> 
 Ste12(Dig1_site, Dig2_site, MAPK_site) + Far1(MAPK_site, S87~none, T306~none)
</modelRxnRule>
*This reaction occurs at a rate that is specified by <modelRxnParam>Sat([[ksynth_Ste12_Far1]],[[Km_synth_Ste12_Far1]])</modelRxnParam></modelRxnFull>

<modelRxnFull><modelRxnRule>
 Ste12(Dig1_site, Dig2_site, MAPK_site) -> 
 Ste12(Dig1_site, Dig2_site, MAPK_site) + Fus3(docking_site, T180~none, Y182~none)
</modelRxnRule>
*This reaction occurs at a rate that is specified by <modelRxnParam>Sat([[ksynth_Ste12_Fus3]],[[Km_synth_Ste12_Fus3]])</modelRxnParam></modelRxnFull>

<modelRxnFull><modelRxnRule>
 Ste12(Dig1_site, Dig2_site, MAPK_site) -> 
 Ste12(Dig1_site, Dig2_site, MAPK_site) + Gpa1(Ste2_site, Ste4_site, nucleotide~GDP)
</modelRxnRule>
*This reaction occurs at a rate that is specified by <modelRxnParam>Sat([[ksynth_Ste12_Gpa1]],[[Km_synth_Ste12_Gpa1]])</modelRxnParam></modelRxnFull>

<modelRxnFull><modelRxnRule>
 Ste12(Dig1_site, Dig2_site, MAPK_site) -> 
 Ste12(Dig1_site, Dig2_site, MAPK_site) + Msg5(MAPK_site)
</modelRxnRule>
*This reaction occurs at a rate that is specified by <modelRxnParam>Sat([[ksynth_Ste12_Msg5]],[[Km_synth_Ste12_Msg5]])</modelRxnParam></modelRxnFull>

<modelRxnFull><modelRxnRule>
 Ste12(Dig1_site, Dig2_site, MAPK_site) -> 
 Ste12(Dig1_site, Dig2_site, MAPK_site) + Ptp(MAPK_site)
</modelRxnRule>
*This reaction occurs at a rate that is specified by <modelRxnParam>Sat([[ksynth_Ste12_Ptp]],[[Km_synth_Ste12_Ptp]])</modelRxnParam></modelRxnFull>

<modelRxnFull><modelRxnRule>
 Ste12(Dig1_site, Dig2_site, MAPK_site) -> 
 Ste12(Dig1_site, Dig2_site, MAPK_site) + Sst2(Ste2_site, MAPK_site, S539~none)
</modelRxnRule>
*This reaction occurs at a rate that is specified by <modelRxnParam>Sat([[ksynth_Ste12_Sst2]],[[Km_synth_Ste12_Sst2]])</modelRxnParam></modelRxnFull>

<modelRxnFull><modelRxnRule>
 Ste12(Dig1_site, Dig2_site, MAPK_site) -> 
 Ste12(Dig1_site, Dig2_site, MAPK_site) + Ste2(Pheromone_site, Gpa1_site, Sst2_site, Yck_site, S338_S339~none)
</modelRxnRule>
*This reaction occurs at a rate that is specified by <modelRxnParam>Sat([[ksynth_Ste12_Ste2]],[[Km_synth_Ste12_Ste2]])</modelRxnParam></modelRxnFull>

<modelRxnFull><modelRxnRule>
 Ste12(Dig1_site, Dig2_site, MAPK_site) -> 
 Ste12(Dig1_site, Dig2_site, MAPK_site) + Ste12(Dig1_site, Dig2_site, MAPK_site)
</modelRxnRule>
*This reaction occurs at a rate that is specified by <modelRxnParam>Sat([[ksynth_Ste12_Ste12]],[[Km_synth_Ste12_Ste12]])</modelRxnParam></modelRxnFull>