Phosphorylation of a P-glycoprotein homologue in Plasmodium falciparum.
A P-glycoprotein homologue has been previously identified in Plasmodium falciparum and was termed PGH 1. This paper describes studies analyzing the phosphorylation of the PGH 1 molecule. It was found, by metabolic labeling with [32P]orthophosphate, that PGH 1 was phosphorylated throughout the entire asexual erythrocytic life cycle of the parasite, with the maximum level of 32P incorporation during the trophozoite and schizont stages. Incubation of trophozoites with modulators of mammalian protein kinases suggests that a Ca(2+)-dependent protein kinase is involved in phosphorylation of PGH 1. PGH 1 could also be phosphorylated in the presence of gamma-32P ATP on purified digestive vacuoles where this protein has previously been localized. Two-dimensional phospho-amino acid analysis revealed that PGH 1 was phosphorylated on serine and threonine residues and the pattern of amino acid phosphorylation was similar for PGH 1 phosphorylated in infected red blood cells and on purified digestive vacuoles. PGH 1 phosphorylation in the presence of some antimalarial drugs was analyzed and it was found that neither chloroquine nor compounds that modulate chloroquine resistance had any effect on PGH 1 phosphorylation.
Lim
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AS
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Cowman
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AF
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000818:Animals; D002118:Calcium; D002352:Carrier Proteins / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D005455:Fluorescent Antibody Technique; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010766:Phosphorylation; D010963:Plasmodium falciparum / Q000254:growth & development / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D013912:Threonine / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D013912:Threonine; D012694:Serine; D011494:Protein Kinases; D002118:Calcium