Cell Cycle Regulation of Signaling
Pheromone signaling arrests cells in G1 phase, prior to the cell cyclecommitment point called“Start”.But once cellspass Start, pheromone signaling is inhibited bythe action of CDKs. We found that the target of this inhibition is Ste5.Specifically, CDKsphosphorylate Ste5 at multiple sites flanking the membrane-binding PM domain, therebydisrupting membrane association. If these sites are mutated to non-phosphorylatable residues(Ste5-8A), then signaling cannot be inhibited during cell cycle progression. Of note,phosphorylation at these sites exerts bulk electrostatic effects such that the magnitude of theinhibitoryeffect is proportional to the number of phosphates added.That is, there is a regulatorycontinuum in which partial phosphorylation yields only partial inhibition.This characteristiccreates opportunities for regulatory diversity in which signaling canbe modulated to varyingdegrees, or perhaps in concert with other regulatory inputs. Such possibilities are being exploredin our current studies.
