Abstract #7

Nuclear translocation of the Hog1 MAP kinase is not necessary for resistance to hyperosmotic stress. Patrick Westfall, Jesse Patterson, Jeremy Thorner. Dept Mol & Cellular Biol, Univ California, Berkeley, Berkeley, CA.
   Survival of all organisms depends on their ability to sense and react appropriately to changing environmental conditions. When external osmolarity is high, S. cerevisiae utilizes a conserved mitogen-activated protein kinase signaling cascade (the High Osmolarity Glycerol or HOG pathway) to evoke appropriate cellular responses. How signal propagation in this MAPK-dependent signaling pathway is regulated is not well understood. Prior work has shown that Hog1 translocates from the cytosol into the nucleus in response to hyperosmotic stress and causes transcriptional induction of many genes. However, we show that preventing nuclear import of Hog1, by tethering it to the plasma membrane and deleting the gene for its nuclear import receptor, still allows cells to grow under hyperosmotic conditions and blocks inappropriate cross-talk with either the mating or invasive growth pathways. Moreover, using DNA microarrays for whole-genome analysis, we have confirmed that preventing Hog1 nuclear import blocks transcription of previously identified hyperosmotic response genes; yet, the cells are able to grow robustly on hyperosmotic medium. Consistent with prior evidence that MAPK phosphatases that act on Hog1 reside in the nucleus, blocking Hog1 nuclear entry retards its down-regulation (dephosphorylation). Collectively, these results indicate, first, that the downstream effectors directly modified by Hog1 that are needed for survival under hyperosmotic conditions and to preserve signaling fidelity must lie at the plasma membrane and/or in the cytosol. Second, that translocation of Hog1 into the nucleus upon hyperosmotic challenge represents primarily a mechanism to down-modulate the enzyme after its initial activation and not, as was previously assumed, to elicit transcriptional responses. Our current focus is to identify both the downstream effectors of Hog1 that are necessary for transmitting the signal that allows cells to survive hyperosmotic challenge and the targets of Hog1 that are responsible for preventing cross-talk between the hyperosmotic stress pathway and other MAPK pathways.

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