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

被引：132

作者：

Alam, Mahmood M. ^{[1
]}

Solyakov, Lev ^{[1
]}

Bottrill, Andrew R. ^{[2
]}

Flueck, Christian ^{[3
]}

Siddiqui, Faiza A. ^{[4
]}

Singh, Shailja ^{[4
]}

Mistry, Sharad ^{[2
]}

Viskaduraki, Maria ^{[5
]}

Lee, Kate ^{[5
]}

Hopp, Christine S. ^{[3
]}

Chitnis, Chetan E. ^{[4
]}

Doerig, Christian ^{[6
]}

Moon, Robert W. ^{[7
]}

Green, Judith L. ^{[7
]}

Holder, Anthony A. ^{[7
]}

Baker, David A. ^{[3
]}

Tobin, Andrew B. ^{[1
]}

机构：

[1] Univ Leicester, MRC Toxicol Unit, Leicester LE1 9HN, Leics, England

[2] Univ Leicester, Core Biotechnol Serv, PNACL, Leicester LE1 9HN, Leics, England

[3] Univ London London Sch Hyg & Trop Med, Fac Infect & Trop Dis, London WC1E 7HT, England

[4] ICGEB, New Delhi 110067, India

[5] Univ Leicester, Core Biotechnol Serv, Bioinformat & Biostat Support Hub B BASH, Leicester LE1 9HN, Leics, England

[6] Monash Univ, Dept Microbiol, Clayton, Vic 3800, Australia

[7] MRC Natl Inst Med Res, Div Parasitol, London NW7 1AA, England

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

HOST-CELL INVASION; PLASMODIUM-FALCIPARUM; SUBSTRATE-SPECIFICITY; PHOSPHORYLATION SITES; ERYTHROCYTE INVASION; STATISTICAL-MODEL; EXPRESSION; IDENTIFICATION; INHIBITORS; GLIDEOSOME;

D O I：

10.1038/ncomms8285

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：15

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