title: Role of the fission yeast cell integrity MAPK pathway in response to glucose limitation.
abstract: BACKGROUND
  Glucose is a signaling molecule which regulates multiple events in eukaryotic organisms and the most preferred carbon source in the fission yeast Schizosaccharomyces pombe. The ability of this yeast to grow in the absence of glucose becomes strongly limited due to lack of enzymes of the glyoxylate cycle that support diauxic growth. The stress-activated protein kinase (SAPK) pathway and its effectors, Sty1 MAPK and transcription factor Atf1, play a critical role in the adaptation of fission yeast to grow on alternative non-fermentable carbon sources by inducing the expression of fbp1+ gene, coding for the gluconeogenic enzyme fructose-1,6-bisphosphatase. The cell integrity Pmk1 pathway is another MAPK cascade that regulates various processes in fission yeast, including cell wall construction, cytokinesis, and ionic homeostasis. Pmk1 pathway also becomes strongly activated in response to glucose deprivation but its role during glucose exhaustion and ensuing adaptation to respiratory metabolism is currently unknown.
  
  
  RESULTS
  We found that Pmk1 activation in the absence of glucose takes place only after complete depletion of this carbon source and that such activation is not related to an endogenous oxidative stress. Notably, Pmk1 MAPK activation relies on de novo protein synthesis, is independent on known upstream activators of the pathway like Rho2 GTPase, and involves PKC ortholog Pck2. Also, the Glucose/cAMP pathway is required operative for full activation of the Pmk1 signaling cascade. Mutants lacking Pmk1 displayed a partial growth defect in respiratory media which was not observed in the presence of glucose. This phenotype was accompanied by a decreased and delayed expression of transcription factor Atf1 and target genes fbp1+ and pyp2+. Intriguingly, the kinetics of Sty1 activation in Pmk1-less cells was clearly altered during growth adaptation to non-fermentable carbon sources.
  
  
  CONCLUSIONS
  Unknown upstream elements mediate Pck2-dependent signal transduction of glucose withdrawal to the cell integrity MAPK pathway. This signaling cascade reinforces the adaptive response of fission yeast to such nutritional stress by enhancing the activity of the SAPK pathway.
authors: Yeast Physiology Group, Department of Genetics and Microbiology, Facultad de Biología, Universidad de Murcia, 30071 Murcia, Spain. marisa@um.es
authors: Marisa
authors: M
authors: Madrid
authors: Jesús
authors: J
authors: Fernández-Zapata
authors: Laura
authors: L
authors: Sánchez-Mir
authors: Teresa
authors: T
authors: Soto
authors: Alejandro
authors: A
authors: Franco
authors: Jero
authors: J
authors: Vicente-Soler
authors: Mariano
authors: M
authors: Gacto
authors: José
authors: J
authors: Cansado
mesh_terms: D015966:Gene Expression Regulation, Fungal; D005947:Glucose / Q000378:metabolism*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D015398:Signal Transduction; D013312:Stress, Physiological
chemical_list: D029702:Schizosaccharomyces pombe Proteins; D020928:Mitogen-Activated Protein Kinases; C516338:Pmk1 protein, S pombe; D048670:MAP Kinase Kinase 4; D005947:Glucose
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