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Phosphoproteomics reveals malaria parasite Protein Kinase G as a signalling hub regulating egress and invasion

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posted on 2015-05-07, 09:57 authored by Mahmood M. Alam, Lev Solyakov, Andrew R. Bottrill, C. Flueck, F. A. Siddiqui, S. Singh, Sharad Mistry, Maria Viskaduraki, Kate Lee, C. S. Hopp, C. E. Chitnis, C. Doerig, R. W. Moon, J. L. Green, A. A. Holder, D. A. Baker, Andrew B. Tobin
Our understanding of the key phosphorylation-dependent signalling pathways in the human malaria parasite, Plasmodium falciparum, remains rudimentary. Here we address this issue for the essential cGMP-dependent protein kinase, PfPKG. By employing chemical and genetic tools in combination with quantitative global phosphoproteomics, we identify the phosphorylation sites on 69 proteins that are direct or indirect cellular targets for PfPKG. These PfPKG targets include proteins involved in cell signalling, proteolysis, gene regulation, protein export and ion and protein transport, indicating that cGMP/PfPKG acts as a signalling hub that plays a central role in a number of core parasite processes. We also show that PfPKG activity is required for parasite invasion. This correlates with the finding that the calcium-dependent protein kinase, PfCDPK1, is phosphorylated by PfPKG, as are components of the actomyosin complex, providing mechanistic insight into the essential role of PfPKG in parasite egress and invasion.


This work has been funded by : ABT - Medical Research Council (Toxicology Unit programme leader), ABT and CD - Wellcome Trust project grant (090313), DAB and ABT. – Wellcome Trust Project Grant (094752). Work in the Holder laboratory was funded by the MRC (File Reference U117532067).



Nature Communications 6:7285

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/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Biological Sciences/Department of Cell Physiology and Pharmacology


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