title: Active nucleocytoplasmic shuttling required for function and regulation of stress-activated kinase Spc1/StyI in fission yeast.
abstract: Transcriptional induction of many stress-response genes is dependent on stress-induced nuclear accumulation of stress-activated protein kinases (SAPKs). In the fission yeast Schizosaccharomyces pombe, nuclear accumulation of the SAPK Spc1 (also known as StyI) requires activating phosphorylation catalyzed by the SAPK kinase Wis1; however, it is unknown whether the localization of Spc1 is regulated by nuclear transport factors. Herein are reported studies that show that Spc1 localization is regulated by active transport mechanisms during osmotic stress. Nuclear import of Spc1 requires Pim1, a homologue of the guanine nucleotide exchange factor RCC1 that is essential for nucleocytoplasmic shuttling of proteins. Nuclear export of Spc1 is regulated by the export factor Crm1. An Spc1-Crm1 complex forms as Spc1 is exported from the nucleus. Wis1 and the tyrosine phosphatases Pyp1 and Pyp2 that inactivate Spc1 are excluded from the nucleus by a Crm1-independent mechanism; hence the nuclear import of Spc1 leads to transient isolation from its regulatory proteins. Thus, active nucleocytoplasmic shuttling is required for both the function and regulation of Spc1 during the osmotic shock response.
authors.affiliation: Departments of Molecular Biology and Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: F
authors.initials: F
authors.lastname: Gaits
authors.forename: P
authors.initials: P
authors.lastname: Russell
mesh_terms: D000957:Antigens, Viral, Tumor / Q000235:genetics / Q000378:metabolism; D001692:Biological Transport; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics* / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D000939:Epitopes; D005656:Fungal Proteins; D016259:Genes, myc; D020662:Guanine Nucleotide Exchange Factors; D028884:Karyopherins; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D009154:Mutation; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins; D012697:Serine Endopeptidases / Q000378:metabolism; D000097606:Exportin 1 Protein
chemical_list: D000957:Antigens, Viral, Tumor; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D000939:Epitopes; D005656:Fungal Proteins; D020662:Guanine Nucleotide Exchange Factors; D028884:Karyopherins; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D017346:Protein Serine-Threonine Kinases; D017027:Protein Tyrosine Phosphatases; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins; D029702:Schizosaccharomyces pombe Proteins; D012697:Serine Endopeptidases; D000097606:Exportin 1 Protein; C490057:pim1 protein, S pombe; C095409:sty1 protein, S pombe; C072068:wis1 protein, S pombe; C097097:pyp1 protein, S pombe; C078759:pyp2 protein, S pombe