Unknown

Dataset Information

0

CDK and MAPK Synergistically Regulate Signaling Dynamics via a Shared Multi-site Phosphorylation Region on the Scaffold Protein Ste5.


ABSTRACT: We report an unanticipated system of joint regulation by cyclin-dependent kinase (CDK) and mitogen-activated protein kinase (MAPK), involving collaborative multi-site phosphorylation of a single substrate. In budding yeast, the protein Ste5 controls signaling through a G1 arrest pathway. Upon cell-cycle entry, CDK inhibits Ste5 via multiple phosphorylation sites, disrupting its membrane association. Using quantitative time-lapse microscopy, we examined Ste5 membrane recruitment dynamics at different cell-cycle stages. Surprisingly, in S phase, where Ste5 recruitment should be blocked, we observed an initial recruitment followed by a steep drop-off. This delayed inhibition revealed a requirement for both CDK activity and negative feedback from the pathway MAPK Fus3. Mutagenesis, mass spectrometry, and electrophoretic analyses suggest that the CDK and MAPK modify shared sites, which are most extensively phosphorylated when both kinases are active and able to bind their docking sites on Ste5. Such collaborative phosphorylation can broaden regulatory inputs and diversify output dynamics of signaling pathways.

SUBMITTER: Repetto MV 

PROVIDER: S-EPMC5858200 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

altmetric image

Publications

CDK and MAPK Synergistically Regulate Signaling Dynamics via a Shared Multi-site Phosphorylation Region on the Scaffold Protein Ste5.

Repetto María Victoria MV   Winters Matthew J MJ   Bush Alan A   Reiter Wolfgang W   Hollenstein David Maria DM   Ammerer Gustav G   Pryciak Peter M PM   Colman-Lerner Alejandro A  

Molecular cell 20180301 6


We report an unanticipated system of joint regulation by cyclin-dependent kinase (CDK) and mitogen-activated protein kinase (MAPK), involving collaborative multi-site phosphorylation of a single substrate. In budding yeast, the protein Ste5 controls signaling through a G1 arrest pathway. Upon cell-cycle entry, CDK inhibits Ste5 via multiple phosphorylation sites, disrupting its membrane association. Using quantitative time-lapse microscopy, we examined Ste5 membrane recruitment dynamics at diffe  ...[more]

Similar Datasets

2018-03-12 | PXD006154 | Pride
| S-EPMC5987779 | biostudies-literature
| S-EPMC6719448 | biostudies-literature
| S-EPMC449765 | biostudies-literature
| S-EPMC2518723 | biostudies-literature
| S-EPMC9271464 | biostudies-literature
| S-EPMC2662209 | biostudies-literature
| S-EPMC6868371 | biostudies-literature
| S-EPMC3631425 | biostudies-literature
| S-EPMC6614033 | biostudies-literature