Mechanical stress impairs pheromone signaling through Pkc1-dependent phosphorylation
Cells integrate multiple external and internal signals, but the underlying cross-talk mechanisms remain unclear. A recent “JCB” paper by the Peter group (IBC) now shows that physical stress activates Pkc1, which in turn inhibits pheromone signaling to prevent cell lysis during yeast mating.
By combining microscopy, microfluidics and classical biochemistry, the Peter group investigated how yeast cells cope with both externally applied and intrinsic mechanical stress during mating. Interestingly, cells exposed to mechanical stress activate Pkc1, which in turn prevents polarized growth by directly phosphorylating the MAP kinase scaffolds Ste5 and Far1 within their conserved RING-H2 domains. Phosphorylation leads to their dissociation from mating projections, thereby inhibiting pheromone signaling. Failure to phosphorylate Ste5 and Far1 during mechanical stress leads to continued pheromone signaling and thus increased cell lysis and defects in cell-cell fusion during mating. These findings identify a molecular mechanism how mechanical stress conditions regulate cell polarity, a process that is implicated in metastasis of tumor cells in higher eukaryotes.
Link to the publication in external pageJournal of Cell Biology