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Nature Research, Nature Communications, 1(6), 2015

DOI: 10.1038/ncomms8285

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

Journal article published in 2015 by Mahmood M. Alam, Lev Solyakov, Andrew R. Bottrill ORCID, Christian Flueck, Faiza A. Siddiqui, Shailja Singh, Sharad Mistry, Maria Viskaduraki, Kate Lee, Christine S. Hopp, Chetan E. Chitnis, Christian Doerig, Robert W. Moon, Judith L. Green, Anthony A. Holder ORCID and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

AbstractOur 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.