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Regulated nucleo/cytoplasmic exchange of HOG1 MAPK requires the importin β homologs NMD5 and XPO1
Author(s) -
Ferrigno Paul,
Posas Francesc,
Koepp Deanna,
Saito Haruo,
Silver Pamela A.
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.19.5606
Subject(s) - biology , importin , microbiology and biotechnology , mitogen activated protein kinase 3 , nuclear transport , nuclear export signal , kinase , map kinase kinase kinase , nuclear localization sequence , mapk/erk pathway , mitogen activated protein kinase kinase , phosphorylation , mitogen activated protein kinase , protein kinase a , cytoplasm , cell nucleus
MAP kinase signaling modules serve to transduce extracellular signals to the nucleus of eukaryotic cells, but little is known about how signals cross the nuclear envelope. Exposure of yeast cells to increases in extracellular osmolarity activates the HOG1 MAP kinase cascade, which is composed of three tiers of protein kinases, namely the SSK2, SSK22 and STE11 MAPKKKs, the PBS2 MAPKK, and the HOG1 MAPK. Using green fluorescent protein (GFP) fusions of these kinases, we found that HOG1, PBS2 and STE11 localize to the cytoplasm of unstressed cells. Following osmotic stress, HOG1, but neither PBS2 nor STE11, translocates into the nucleus. HOG1 translocation occurs very rapidly, is transient, and correlates with the phosphorylation and activation of the MAP kinase by its MAPKK. HOG1 phosphorylation is necessary and sufficient for nuclear translocation, because a catalytically inactive kinase when phosphorylated is translocated to the nucleus as efficiently as the wild‐type. Nuclear import of the MAPK under stress conditions requires the activity of the small GTP binding protein Ran–GSP1, but not the NLS‐binding importin α/β heterodimer. Rather, HOG1 import requires the activity of a gene, NMD5 , that encodes a novel importin β homolog. Similarly, export of dephosphorylated HOG1 from the nucleus requires the activity of the NES receptor XPO1/CRM1. Our findings define the requirements for the regulated nuclear transport of a stress‐activated MAP kinase.