Open AccessPhosphoproteomic analyses reveal novel cross‐modulation mechanisms between two signaling pathways in yeast
Author(s) -
Vaga Stefania,
BernardoFaura Marti,
Cokelaer Thomas,
Maiolica Alessio,
Barnes Christopher A,
Gillet Ludovic C,
Hegemann Björn,
Drogen Frank,
Sharifian Hoda,
Klipp Edda,
Peter Matthias,
SaezRodriguez Julio,
Aebersold Ruedi
Publication year - 2014
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.15252/msb.20145112
Subject(s) - biology , phosphoproteomics , phosphorylation , crosstalk , signal transduction , microbiology and biotechnology , protein phosphorylation , kinase , proteomics , protein kinase a , biochemistry , gene , physics , optics
Cells respond to environmental stimuli via specialized signaling pathways. Concurrent stimuli trigger multiple pathways that integrate information, predominantly via protein phosphorylation. Budding yeast responds to NaCl and pheromone via two mitogen‐activated protein kinase cascades, the high osmolarity, and the mating pathways, respectively. To investigate signal integration between these pathways, we quantified the time‐resolved phosphorylation site dynamics after pathway co‐stimulation. Using shotgun mass spectrometry, we quantified 2,536 phosphopeptides across 36 conditions. Our data indicate that NaCl and pheromone affect phosphorylation events within both pathways, which thus affect each other at more levels than anticipated, allowing for information exchange and signal integration. We observed a pheromone‐induced down‐regulation of Hog1 phosphorylation due to Gpd1, Ste20, Ptp2, Pbs2, and Ptc1. Distinct Ste20 and Pbs2 phosphosites responded differently to the two stimuli, suggesting these proteins as key mediators of the information exchange. A set of logic models was then used to assess the role of measured phosphopeptides in the crosstalk. Our results show that the integration of the response to different stimuli requires complex interconnections between signaling pathways.