Project Details
Projekt
Cross-talk between CDK and PKA signaling
Subject Area
Cell Biology
Biochemistry
Biochemistry
Term
from 2019 to 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 426546316
A cell is constantly receiving signals from its environment and from intracellular processes including nutrient sensors, stress response pathways, or the cell cycle machinery. These signals need to be integrated into coordinated physiological responses. Signal integration can occur for example through cross-talk of kinase pathways or through multi-site phosphorylation of target proteins. Two of the most important globally acting kinases in baker’s yeast are the cyclin-dependent kinase, which regulates the cell cycle, and the protein kinase A, which regulates carbon metabolism, growth, and general stress responses. Evidence suggests that there is cross-talk between these two kinase pathways to coordinate metabolism, growth, and division. However, the molecular mechanisms coordinating CDK and PKA signaling remain largely unexplored.Here, I propose to mechanistically determine how two of the yeast cell’s global signaling pathways are integrated to determine cellular physiology. By combining biochemistry, mass spectrometry, genetics, yeast physiology and live cell imaging, we will investigate the cross-talk between the CDK and PKA pathways in three different ways: Firstly, we will investigate how these kinases jointly regulate our model substrate, the trehalose degrading enzyme Nth1. This enzyme can be phosphorylated on at least four PKA and one CDK sites, but the function and interdependency of these site are still unclear. Secondly, using Nth1 and other models we will elucidate if and how PKA can generate docking motifs for CDK, and thus alter the binding of CDK to its substrates. Thirdly, we will determine if and how CDK regulates the PKA pathway during the cell cycle, based on evidence from a recently generated phosphoproteome data set. Unraveling the CDK-PKA interface from these different angles will further advance our understanding of how the cell coordinates different (potentially conflicting) aims during growth and the cell cycle in different environments.
DFG Programme
Research Grants
