title: PhosphoTyrosyl phosphatase activator of Plasmodium falciparum: identification of its residues involved in binding to and activation of PP2A.
abstract: In Plasmodium falciparum (Pf), the causative agent of the deadliest form of malaria, a tight regulation of phosphatase activity is crucial for the development of the parasite. In this study, we have identified and characterized PfPTPA homologous to PhosphoTyrosyl Phosphatase Activator, an activator of protein phosphatase 2A which is a major phosphatase involved in many biological processes in eukaryotic cells. The PfPTPA sequence analysis revealed that five out of six amino acids involved in interaction with PP2A in human are conserved in P. falciparum. Localization studies showed that PfPTPA and PfPP2A are present in the same compartment of blood stage parasites, suggesting a possible interaction of both proteins. In vitro binding and functional studies revealed that PfPTPA binds to and activates PP2A. Mutation studies showed that three residues (V(283), G(292) and M(296)) of PfPTPA are indispensable for the interaction and that the G(292) residue is essential for its activity. In P. falciparum, genetic studies suggested the essentiality of PfPTPA for the completion of intraerythrocytic parasite lifecycle. Using Xenopus oocytes, we showed that PfPTPA blocked the G2/M transition. Taken together, our data suggest that PfPTPA could play a role in the regulation of the P. falciparum cell cycle through its PfPP2A regulatory activity.
authors: Center for Infection and Immunity of Lille, Inserm U1019-CNRS UMR 8204, University of Lille Nord de France, Institut Pasteur de Lille, 1 Rue du Professeur Calmette, Lille 59019, Cedex, France. audrey.vandomme@pasteur-lille.fr.
authors: Audrey
authors: A
authors: Vandomme
authors: Center for Infection and Immunity of Lille, Inserm U1019-CNRS UMR 8204, University of Lille Nord de France, Institut Pasteur de Lille, 1 Rue du Professeur Calmette, Lille 59019, Cedex, France. alinekatia.freville@gmail.com.
authors: Aline
authors: A
authors: Fréville
authors: EA4479, IFR147, Laboratoire de Régulation des Signaux de Division, SN3, Université des Sciences et Technologies de Lille, Villeneuve d'Ascq 59655, France. katia.maggio@univ-lille1.fr.
authors: Katia
authors: K
authors: Cailliau
authors: Center for Infection and Immunity of Lille, Inserm U1019-CNRS UMR 8204, University of Lille Nord de France, Institut Pasteur de Lille, 1 Rue du Professeur Calmette, Lille 59019, Cedex, France. hkalamou@gmail.com.
authors: Hadidjatou
authors: H
authors: Kalamou
authors: EA4479, IFR147, Laboratoire de Régulation des Signaux de Division, SN3, Université des Sciences et Technologies de Lille, Villeneuve d'Ascq 59655, France. Jean-Francois.Bodart@univ-lille1.fr.
authors: Jean-François
authors: JF
authors: Bodart
authors: Center for Infection and Immunity of Lille, Inserm U1019-CNRS UMR 8204, University of Lille Nord de France, Institut Pasteur de Lille, 1 Rue du Professeur Calmette, Lille 59019, Cedex, France. jamal.khalife@pasteur-lille.fr.
authors: Jamal
authors: J
authors: Khalife
authors: Center for Infection and Immunity of Lille, Inserm U1019-CNRS UMR 8204, University of Lille Nord de France, Institut Pasteur de Lille, 1 Rue du Professeur Calmette, Lille 59019, Cedex, France. christine.pierrot@pasteur-lille.fr.
authors: Christine
authors: C
authors: Pierrot
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002453:Cell Cycle / Q000235:genetics; D003001:Cloning, Molecular; D004789:Enzyme Activation; D015870:Gene Expression; D023061:Gene Order; D018390:Gene Targeting; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009865:Oocytes / Q000378:metabolism; D010802:Phylogeny; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014981:Xenopus
chemical_list: D015800:Protozoan Proteins; D054648:Protein Phosphatase 2