DSpace@MIT (Massachusetts Institute of Technology) · 2013 · 108 citations · 15 references
Open access
Life SciencesCell BiologyMolecular BiologyCell SignalingMolecular Cell BiologySignal TransductionCell Cycle ControlCell Cycle SignalingCell-cycle RegulationProtein Kinase CascadesScaffold ProteinsSignal Transduction PathwaysG1-s Phase TransitionHippo SignalingHippo Signaling PathwayPhosphorylation-dependent RegulationScaffold Proteins In Kinase CascadesScaffold Proteins In Signal TransductionScaffold Proteins In SignalingSignal Transduction Pathway Activation
Scaffold-assisted signaling cascades guide cellular decision-making. In budding yeast, one such signal transduction pathway called the mitotic exit network (MEN) governs the transition from mitosis to the G1 phase of the cell cycle. The MEN is conserved and in metazoans is known as the Hippo tumor-suppressor pathway. We found that signaling through the MEN kinase cascade was mediated by an unusual two-step process. The MEN kinase Cdc15 first phosphorylated the scaffold Nud1. This created a phospho-docking site on Nud1, to which the effector kinase complex Dbf2-Mob1 bound through a phosphoserine-threonine binding domain, in order to be activated by Cdc15. This mechanism of pathway activation has implications for signal transmission through other kinase cascades and might represent a general principle in scaffold-assisted signaling.
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Andre Levchenko, Jehoshua Bruck, Paul W. Sternberg · Proceedings of the National Academy of Sciences · 2000 · 498 citations