Biological significance of nuclear localization of mitogen-activated protein kinase Pmk1 in fission yeast.
Mitogen-activated protein kinase (MAPK) signaling pathways play a fundamental role in the response of eukaryotic cells to environmental changes. Also, much evidence shows that the stimulus-dependent nuclear targeting of this class of regulatory kinases is crucial for adequate regulation of distinct cellular events. In the fission yeast Schizosaccharomyces pombe, the cell integrity MAPK pathway, whose central element is the MAPK Pmk1, regulates multiple processes such as cell wall integrity, vacuole fusion, cytokinesis, and ionic homeostasis. In non-stressed cells Pmk1 is constitutively localized in both cytoplasm and nucleus, and its localization pattern appears unaffected by its activation status or in response to stress, thus questioning the biological significance of the presence of this MAPK into the nucleus. We have addressed this issue by characterizing mutants expressing Pmk1 versions excluded from the cell nucleus and anchored to the plasma membrane in different genetic backgrounds. Although nuclear Pmk1 partially regulates cell wall integrity at a transcriptional level, membrane-tethered Pmk1 performs many of the biological functions assigned to wild type MAPK like regulation of chloride homeostasis, vacuole fusion, and cellular separation. However, we found that down-regulation of nuclear Pmk1 by MAPK phosphatases induced by the stress activated protein kinase pathway is important for the fine modulation of extranuclear Pmk1 activity. These results highlight the importance of the control of MAPK activity at subcellular level.
Yeast Physiology Group, Department of Genetics and Microbiology, Facultad de Biología. Universidad de Murcia, 30071 Murcia, Spain.
Laura
L
Sánchez-Mir
Alejandro
A
Franco
Marisa
M
Madrid
Jero
J
Vicente-Soler
M Antonia
MA
Villar-Tajadura
Teresa
T
Soto
Pilar
P
Pérez
Mariano
M
Gacto
José
J
Cansado
D021581:Active Transport, Cell Nucleus; D020816:Amino Acid Motifs; D002455:Cell Division; D002467:Cell Nucleus / Q000201:enzymology*; D002473:Cell Wall / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis; D008561:Membrane Fusion; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000201:enzymology* / Q000378:metabolism / Q000502:physiology; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological; D014617:Vacuoles / Q000378:metabolism
D002712:Chlorides; D011993:Recombinant Fusion Proteins; D029702:Schizosaccharomyces pombe Proteins; D049452:Green Fluorescent Proteins; D020928:Mitogen-Activated Protein Kinases; C516338:Pmk1 protein, S pombe