Anion channels in Plasmodium-falciparum-infected erythrocytes and protein kinase A

Anaïs Merckx1, Guillaume Bouyer 2, Serge L.Y. Thomas2, Gordon Langsley 1 and Stéphane Egée2

1 Institut Cochin, INSERM U567, Université Paris Descartes, CNRS (UMR 8104), Paris, France

2 Université Pierre et Marie Curie Paris 6 – CNRS UMR7150 Station Biologique, BP 74, 29682 Roscoff Cedex, France

Corresponding author: Egée, S. ().

Supplementary Table 1. Putative PKA substrates among transporters identified in the human erythrocyte proteome

Name / Accession number / Putative PKA phosphorylation sitesa
ATP-binding cassette half-transporter / AAG33617 / +
Multidrug resistance-associated protein 6 / O95255 / +
ATP-binding cassette, sub-family G, member 2 / NP_004818 / +
Multidrug resistance-associated protein 4 / O15439 / +
Plasma membrane calcium-transporting ATPase 4 / P23634 / -
Sodium/potassium-transporting ATPase subunit alpha-2 precursor / P50993 / -
Glucose transporter type 1 (GLUT-1) / P11166 / -
Solute carrier family 2 (facilitated glucose transporter), member 3 / NP_008862 / -
Glucose transporter / AAK31911 / +
Solute carrier family 1 (glutamate transporter), member 7 / NP_006662 / -
Solute carrier family 27 (fatty acid transporter), member 4 / NP_005085 / -
Solute carrier family 29 (nucleoside transporters), member 1 / CAI20093 / -
Solute carrier family 40 member 1 (Ferroportin-1) / Q9NP59 / -
Monocarboxylate transporter 1 (MCT 1) / P53985 / -
Solute carrier family 5 (choline transporter), member 7 / NP_068587 / -
Solute carrier family 9 isoform 3 regulator 2 (NHE1) / NP_004776 / +
Solute carrier family 12 (potassium/chloride transporters), member 4 (KCC1) / NP_005063 / +
Band 3 anion transport protein / P02730 / -
Chloride intracellular channel protein 3 / O95833 / -
Intermediate conductance calcium-activated potassium channel protein 1 / NP_002241 / +
Potassium channel subfamily K member 5 / O95279 / +
Cystic fibrosis transmembrane conductance regulator (CFTR) b / P13569 / +
Chloride Channel CLC-2 b / NP_004357 / +
Short transient receptor potential channel 6 (TrpC6) b / Q9Y210 / +

aAn in silico search [1] was performed using PkaPS (http://mendel.imp.ac.at/sat/pkaPS/pkaPS.html) for PKA phosphorylation sites in putative transporters and channels listed in both the human erythrocyte proteome. As PfPKA activates anion transport through the erythrocyte membrane, the RBC proteome [2-4] was first examined for channels and transporters and to substantiate the predictions and the literature was checked for known PKA substrates in such proteins as the ATP binding cassette transporter [5]. Gray highlighting and ‘+’ indicate transporters for which a score above 1 have been found using PkaPS script. ‘-’ indicates transporters for which a score below 1 was found using PkaPS script.

bProteins for which biochemical or electrophysiological evidences are reported in the literature, but not found in any publicly available RBC proteome.

References

1 Neuberger, G. et al. (2007) pkaPS: prediction of protein kinase A phosphorylation sites with the simplified kinase-substrate binding model. Biol Direct 2, 1

2 Goodman, S.R. et al. (2007) The human red blood cell proteome and interactome. Exp Biol Med (Maywood) 232 (11), 1391-1408

3 Pasini, E.M. et al. (2006) In-depth analysis of the membrane and cytosolic proteome of red blood cells. Blood 108 (3), 791-801

4 Roux-Dalvai, F. et al. (2008) Extensive analysis of the cytoplasmic proteome of human erythrocytes using the peptide ligand library technology and advanced mass spectrometry. Mol Cell Proteomics 7, 2254-2269

5 Abraham, E.H. et al. (2001) Erythrocyte membrane ATP binding cassette (ABC) proteins: MRP1 and CFTR as well as CD39 (ecto-apyrase) involved in RBC ATP transport and elevated blood plasma ATP of cystic fibrosis. Blood Cells Mol Dis 27 (1), 165-180.

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