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

Alam, M. M. et al. (2015) Phosphoproteomics reveals malaria parasite Protein Kinase G as a signalling hub regulating egress and invasion. Nature Communications, 6, 7285. (doi: 10.1038/ncomms8285) (PMID:26149123) (PMCID:PMC4507021)

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Abstract

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Tobin, Andrew and Alam, Dr Mahmood
Authors: Alam, M. M., Solyakov, L., Bottrill, A. R., Flueck, C., Siddiqui, F. A., Singh, S., Mistry, S., Viskaduraki, M., Lee, K., Hopp, C. S., Chitnis, C. E., Doerig, C., Moon, R. W., Green, J. L., Holder, A. A., Baker, D. A., and Tobin, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Nature Communications
Publisher:Nature Communications
ISSN:2041-1723
ISSN (Online):2041-1723
Published Online:07 July 2015
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Nature Communications 6:7285
Publisher Policy:Reproduced under a Creative Commons License

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