REGULATED NUCLEO CYTOPLASMIC EXCHANGE OF HOG1 MAPK REQUIRES THE IMPORTIN-BETA HOMOLOGS NMD5 AND XPO1/

MAP kinase signaling modules serve to transduce extracellular signals to the nucleus of eukaryotic cells, but little is known about how sign als cross the nuclear envelope, Exposure of yeast tells to increases i n extracellular osmolarity activates the HOG1 MAP kinase cascade, whic h is composed of three tiers of protein kinases, namely the SSK2, SSK2 2 and STE11 MAP-KKKs, the PBS2 MAPKK, and the HOG1 MAPK, Using green f luorescent protein (GFP) fusions of these kinases, we found that HOG1, PBS2 and STE11 localize to the cytoplasm of unstressed cells, Followi ng osmotic stress, HOG1, but neither PBS2 nor STE11, translocates into the nucleus. HOG1 translocation occurs very rapidly, is transient, an d correlates with the phosphorylation and activation of the MAP kinase by its MAPKK, HOG1 phosphorylation is necessary and sufficient for nu clear translocation, because a catalytically inactive kinase when phos phorylated is translocated to the nucleus as efficiently as the wild-t ype. Nuclear import of the MAPK under stress conditions requires the a ctivity of the small GTP binding protein Ran-GSP1, but not the NLS-bin ding importin alpha/beta heterodimer, Rather, HOG1 import requires the activity of a gene, NMD5, that encodes a novel importin beta homolog, Similarly, export of dephosphorylated HOG1 from the nucleus requires the activity of the NES receptor XPO1/CRM1, Our findings define the re quirements For the regulated nuclear transport of a stress-activated M AP kinase.