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J Cell Biol

Title:		Mechanical stress impairs pheromone signaling via Pkc1-mediated regulation of the MAPK scaffold Ste5
Author(s):		Van Drogen F; Mishra R; Rudolf F; Walczak MJ; Lee SS; Reiter W; Hegemann B; Pelet S; Dohnal I; Binolfi A; Yudina Z; Selenko P; Wider G; Ammerer G; Peter M;
Address:		"Institute for Biochemistry, ETH Zurich, Zurich, Switzerland vafrank@ethz.ch. Institute for Biochemistry, ETH Zurich, Zurich, Switzerland. Institute of Molecular Biology and Biophysics, ETH Zurich, Zurich, Switzerland. Scientific Center for Optical and Electron Microscopy, ETH Zurich, Zurich, Switzerland. Department of Biochemistry, Max F. Perutz Laboratories, University of Vienna, Vienna, Austria. Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland. Department of Nuclear Magnetic Resonance-Supported Structural Biology, Leibniz Institute of Molecular Pharmacology, Berlin, Germany. Institute for Biochemistry, ETH Zurich, Zurich, Switzerland matthias.peter@bc.biol.ethz.ch"
Journal Title:		J Cell Biol
Year:		2019
Volume:		20190717
Issue:		9
Page Number:		3117 - 3133
DOI:		10.1083/jcb.201808161
ISSN/ISBN:		1540-8140 (Electronic) 0021-9525 (Print) 0021-9525 (Linking)
Abstract:		"Cells continuously adapt cellular processes by integrating external and internal signals. In yeast, multiple stress signals regulate pheromone signaling to prevent mating under unfavorable conditions. However, the underlying crosstalk mechanisms remain poorly understood. Here, we show that mechanical stress activates Pkc1, which prevents lysis of pheromone-treated cells by inhibiting polarized growth. In vitro Pkc1 phosphorylates conserved residues within the RING-H2 domains of the scaffold proteins Far1 and Ste5, which are also phosphorylated in vivo. Interestingly, Pkc1 triggers dispersal of Ste5 from mating projections upon mechanically induced stress and during cell-cell fusion, leading to inhibition of the MAPK Fus3. Indeed, RING phosphorylation interferes with Ste5 membrane association by preventing binding to the receptor-linked Gbetagamma protein. Cells expressing nonphosphorylatable Ste5 undergo increased lysis upon mechanical stress and exhibit defects in cell-cell fusion during mating, which is exacerbated by simultaneous expression of nonphosphorylatable Far1. These results uncover a mechanical stress-triggered crosstalk mechanism modulating pheromone signaling, polarized growth, and cell-cell fusion during mating"
Keywords:		"Adaptor Proteins, Signal Transducing/genetics/*metabolism Cyclin-Dependent Kinase Inhibitor Proteins/genetics/metabolism Mitogen-Activated Protein Kinases/genetics/metabolism Phosphorylation/genetics Protein Kinase C/genetics/*metabolism Saccharomyces cer;"
Notes:		"Medlinevan Drogen, Frank Mishra, Ranjan Rudolf, Fabian Walczak, Michal J Lee, Sung Sik Reiter, Wolfgang Hegemann, Bjorn Pelet, Serge Dohnal, Ilse Binolfi, Andres Yudina, Zinaida Selenko, Philipp Wider, Gerhard Ammerer, Gustav Peter, Matthias eng Research Support, Non-U.S. Gov't 2019/07/19 J Cell Biol. 2019 Sep 2; 218(9):3117-3133. doi: 10.1083/jcb.201808161. Epub 2019 Jul 17"