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Molecular mechanisms controlling phosphate-induced downregulation of the yeast Pho84 phosphate transporter

Lundh, Fredrik; Mouillon, Jean-Marie; Samyn, Dieter; Stadler, Kent; Popova, Yulia; Lagerstedt, Jens O LU ; Thevelein, Johan M and Persson, Bengt L (2009) In Biochemistry 48(21). p.505-4497
Abstract

In Saccharomyces cerevisiae, phosphate uptake is mainly dependent on the proton-coupled Pho84 permease under phosphate-limited growth conditions. Phosphate addition causes Pho84-mediated activation of the protein kinase A (PKA) pathway as well as rapid internalization and vacuolar breakdown of Pho84. We show that Pho84 undergoes phosphate-induced phosphorylation and subsequent ubiquitination on amino acids located in the large middle intracellular loop prior to endocytosis. The attachment of ubiquitin is dependent on the ubiquitin conjugating enzymes Ubc2 and Ubc4. In addition, we show that the Pho84 endocytotic process is delayed in strains with reduced PKA activity. Our results suggest that Pho84-mediated activation of the PKA pathway... (More)

In Saccharomyces cerevisiae, phosphate uptake is mainly dependent on the proton-coupled Pho84 permease under phosphate-limited growth conditions. Phosphate addition causes Pho84-mediated activation of the protein kinase A (PKA) pathway as well as rapid internalization and vacuolar breakdown of Pho84. We show that Pho84 undergoes phosphate-induced phosphorylation and subsequent ubiquitination on amino acids located in the large middle intracellular loop prior to endocytosis. The attachment of ubiquitin is dependent on the ubiquitin conjugating enzymes Ubc2 and Ubc4. In addition, we show that the Pho84 endocytotic process is delayed in strains with reduced PKA activity. Our results suggest that Pho84-mediated activation of the PKA pathway is responsible for its own downregulation by phosphorylation, ubiquination, internalization, and vacuolar breakdown.

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Contribution to journal
publication status
published
keywords
Cyclic AMP-Dependent Protein Kinases, Down-Regulation, Feedback, Physiological, Intracellular Space, Phosphates, Phosphorylation, Protein Transport, Proton-Phosphate Symporters, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Signal Transduction, Ubiquitin, Up-Regulation, Journal Article, Research Support, Non-U.S. Gov't
in
Biochemistry
volume
48
issue
21
pages
9 pages
publisher
The American Chemical Society
external identifiers
  • scopus:66349086108
ISSN
0006-2960
DOI
10.1021/bi9001198
language
English
LU publication?
no
id
0c5dd5c8-53a2-4bc3-a6f1-b1b4de3264a3
date added to LUP
2017-10-19 20:09:42
date last changed
2017-10-23 10:13:50
@article{0c5dd5c8-53a2-4bc3-a6f1-b1b4de3264a3,
  abstract     = {<p>In Saccharomyces cerevisiae, phosphate uptake is mainly dependent on the proton-coupled Pho84 permease under phosphate-limited growth conditions. Phosphate addition causes Pho84-mediated activation of the protein kinase A (PKA) pathway as well as rapid internalization and vacuolar breakdown of Pho84. We show that Pho84 undergoes phosphate-induced phosphorylation and subsequent ubiquitination on amino acids located in the large middle intracellular loop prior to endocytosis. The attachment of ubiquitin is dependent on the ubiquitin conjugating enzymes Ubc2 and Ubc4. In addition, we show that the Pho84 endocytotic process is delayed in strains with reduced PKA activity. Our results suggest that Pho84-mediated activation of the PKA pathway is responsible for its own downregulation by phosphorylation, ubiquination, internalization, and vacuolar breakdown.</p>},
  author       = {Lundh, Fredrik and Mouillon, Jean-Marie and Samyn, Dieter and Stadler, Kent and Popova, Yulia and Lagerstedt, Jens O and Thevelein, Johan M and Persson, Bengt L},
  issn         = {0006-2960},
  keyword      = {Cyclic AMP-Dependent Protein Kinases,Down-Regulation,Feedback, Physiological,Intracellular Space,Phosphates,Phosphorylation,Protein Transport,Proton-Phosphate Symporters,Saccharomyces cerevisiae,Saccharomyces cerevisiae Proteins,Signal Transduction,Ubiquitin,Up-Regulation,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  month        = {06},
  number       = {21},
  pages        = {505--4497},
  publisher    = {The American Chemical Society},
  series       = {Biochemistry},
  title        = {Molecular mechanisms controlling phosphate-induced downregulation of the yeast Pho84 phosphate transporter},
  url          = {http://dx.doi.org/10.1021/bi9001198},
  volume       = {48},
  year         = {2009},
}