A processive phosphorylation circuit with multiple kinase inputs and mutually diversional routes controls G1/S decision.

摘要: Studies on multisite phosphorylation networks of cyclin-dependent kinase (CDK) targets have opened a new level signaling complexity by revealing signal processing routes encoded into disordered proteins. A model target, the CDK inhibitor Sic1, contains linear motifs, docking sites, and phosphodegrons to empower an N-to-C terminally directed process. Here, we uncover mechanism involving multi-step competition between mutually diversional within S-CDK-Sic1 inhibitory complex. Intracomplex plays direct role in controlling Sic1 degradation, provides sequentially integrate both G1- S-CDK activities while keeping inhibited towards other targets. The competing prevent premature degradation demonstrate how integration MAPK from pheromone pathway allows one tune alternative paths. circuits may be general way for multiple signals coordinate cellular decisions eukaryotes.