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Dynamic Studies of Scaffold-Dependent Mating Pathway in Yeast

Danying Shao ^* , Wen Zheng ^* , Wenjun Qiu ^* , Qi Ouyang ^*  and Chao Tang ^*  

^* Center for Theoretical Biology and Department of Physics, Peking University, Beijing, China; and California Institute for Quantitative Biomedical Research, Departments of Biopharmaceutical Sciences and Biochemistry and Biophysics, University of California at San Francisco, San Francisco, California

Correspondence: Address reprint requests to Qi Ouyang, E-mail: qi{at}pku.edu.cn; or Chao Tang, E-mail: chao.tang{at}ucsf.edu.

The mating pathway in Saccharomyces cerevisiae is one of the best understood signal transduction pathways in eukaryotes. It transmits the mating signal from plasma membrane into the nucleus through the G-protein coupled receptor and the mitogen-activated protein kinase (MAPK) cascade. According to current understanding of the mating pathway, we construct a system of ordinary differential equations to describe the process. Our model is consistent with a wide range of experiments, indicating that it captures some main characteristics of the signal transduction along the pathway. Investigation with the model reveals that the shuttling of the scaffold protein and the dephosphorylation of kinases involved in the MAPK cascade cooperate to regulate the response upon pheromone induction and to help preserve the fidelity of the mating signaling. We explored factors affecting the dose-response curves of this pathway and found that both negative feedback and concentrations of the proteins involved in the MAPK cascade play crucial roles. Contrary to some other MAPK systems where signaling sensitivity is being amplified successively along the cascade, here the mating signal is transmitted through the cascade in an almost linear fashion.

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