PXD006154

PXD006154 is an original dataset announced via ProteomeXchange.

Title	CDK and MAPK collaborate to regulate signaling dynamics via multi-site phosphorylation of the scaffold protein Ste5
Description	CDKs and MAPKs phosphorylate similar sites yet generally have distinct functions/substrates. We report here an unanticipated system of cooperative regulation by CDK and MAPK, involving collaborative multi-site phosphorylation of a single substrate. The budding yeast protein Ste5 is a signaling scaffold for the pheromone-activated G1 arrest pathway. Upon cell cycle entry, CDK activity inhibits Ste5 via phosphorylation at numerous sites flanking its membrane-binding domain. Ste5 is also regulated by negative feedback from the pathway MAPK, though the mechanism was unknown. Using quantitative time-lapse microscopy, we examined Ste5 membrane recruitment dynamics at different cell cycle stages. Surprisingly, at stages where we expected Ste5 recruitment would be blocked, we observed transient recruitment followed by a steep decline, depending on both CDK and MAPK activities. The collective results of mutagenesis, mass spectrometry, and electrophoretic analyses suggest that the CDK and MAPK target shared sites, and that the substrate is most extensively phosphorylated when both kinases are active and able to bind their respective docking sites on Ste5. This collaborative phosphorylation can diversify regulatory options, ranging from mild tuning to strong blocking, and can yield distinct patterns of regulatory dynamics at different cell cycle stages.
HostingRepository	PRIDE
AnnounceDate	2018-03-12
AnnouncementXML	Submission_2018-03-20_04:30:56.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Wolfgang Reiter
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-03-22 04:39:06	ID requested
1	2018-03-12 07:58:14	announced
⏵ 2	2018-03-20 04:30:58	announced	Updated publication reference for PubMed record(s): 29547722.

Repetto MV, Winters MJ, Bush A, Reiter W, Hollenstein DM, Ammerer G, Pryciak PM, Colman-Lerner A, CDK and MAPK Synergistically Regulate Signaling Dynamics via a Shared Multi-site Phosphorylation Region on the Scaffold Protein Ste5. Mol Cell, 69(6):938-952.e6(2018) [pubmed]

curator keyword: Biological

submitter keyword: Yeast, Ste5, MAPK, CDK, pheromone response, phospho proteomics

Wolfgang Reiter
contact affiliation	Department for Biochemistry, Max F. Perutz Laboratories, University of Vienna, Dr. Bohr-Gasse 9, A-1030 Vienna, Austria
contact email	wolfgang.l.reiter@univie.ac.at
lab head
Wolfgang Reiter
contact affiliation	MAX F. PERUTZ LABORATORIES - University of Vienna
contact email	wolfgang.l.reiter@univie.ac.at
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD006154
     1. Label: PRIDE project
     2. Name: CDK and MAPK collaborate to regulate signaling dynamics via multi-site phosphorylation of the scaffold protein Ste5