Inhibition of the protein kinase A alters the degradation of the high-affinity phosphate transporter Pho84 in Saccharomyces cerevisiae.
In Saccharomyces cerevisiae, nutrient sensing is the major factor controlling cell growth and proliferation. It has been shown that phosphate signalling involves the activation of the protein kinase A (PKA) in response to an elevation of external phosphate when cells have experienced a severe phosphate limitation. Addition of phosphate or its non-metabolized analogue, methylphosphonate (MP), to cells grown under phosphate limitation triggers degradation of the Pho84 phosphate transporter and represses the acidic phosphatase activity. In this study we have shown that of the five inorganic phosphate transporters (Pho84, Pho87, Pho89, Pho90, Pho91) of the plasma membrane, only Pho84 is required for the MP recognition and repression of the acidic phosphatase activity. By use of the PKA inhibitor H89, we demonstrate that down-regulation and degradation of the Pho84 transporter, in response to an elevation of external phosphate, is delayed by the inhibition of PKA. In contrast, down-regulation of the acidic phosphatase is under these conditions not affected by the PKA inhibition. Altogether, these observations suggest that the PKA signalling pathway plays a role in conveying the signal for the down-regulation and degradation of the Pho84 transporter in the vacuolar compartment in response to altered phosphate availability in the external environment.
Mouillon
Jean-Marie
JM
Department of Chemistry and Biomedical Sciences, Kalmar University, 391 82, Kalmar, Sweden.
Persson
Bengt L
BL
D000135:Acid Phosphatase / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015536:Down-Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007546:Isoquinolines / Q000378:metabolism / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000378:metabolism / Q000494:pharmacology; D028061:Phosphate Transport Proteins / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D028081:Proton-Phosphate Symporters / Q000187:drug effects / Q000378:metabolism*; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000378:metabolism / Q000494:pharmacology; D013997:Time Factors
D007546:Isoquinolines; D009943:Organophosphorus Compounds; C105495:PHO84 protein, S cerevisiae; D028061:Phosphate Transport Proteins; D010710:Phosphates; D028081:Proton-Phosphate Symporters; D029701:Saccharomyces cerevisiae Proteins; D013449:Sulfonamides; D049452:Green Fluorescent Proteins; C032627:methylphosphonic acid; D017868:Cyclic AMP-Dependent Protein Kinases; D000135:Acid Phosphatase; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide