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 (V283, G292 and M296) of PfPTPA are indispensable for the interaction and that the G292 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.
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Vandomme, A.; Fréville, A.; Cailliau, K.; Kalamou, H.; Bodart, J.-F.; Khalife, J.; Pierrot, C. PhosphoTyrosyl Phosphatase Activator of Plasmodium falciparum: Identification of Its Residues Involved in Binding to and Activation of PP2A. Int. J. Mol. Sci. 2014, 15, 2431-2453.
Vandomme A, Fréville A, Cailliau K, Kalamou H, Bodart J-F, Khalife J, Pierrot C. PhosphoTyrosyl Phosphatase Activator of Plasmodium falciparum: Identification of Its Residues Involved in Binding to and Activation of PP2A. International Journal of Molecular Sciences. 2014; 15(2):2431-2453.
Vandomme, Audrey; Fréville, Aline; Cailliau, Katia; Kalamou, Hadidjatou; Bodart, Jean-François; Khalife, Jamal; Pierrot, Christine. 2014. "PhosphoTyrosyl Phosphatase Activator of Plasmodium falciparum: Identification of Its Residues Involved in Binding to and Activation of PP2A." Int. J. Mol. Sci. 15, no. 2: 2431-2453.