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The systematic functional analysis of Plasmodium protein kinases identifies essential regulators of mosquito transmission
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2010 (English)In: Cell Host and Microbe, ISSN 1931-3128, E-ISSN 1934-6069, Vol. 8, no 4, p. 377-387Article in journal (Refereed) Published
Abstract [en]

Although eukaryotic protein kinases (ePKs) contribute to many cellular processes, only three Plasmodium falciparum ePKs have thus far been identified as essential for parasite asexual blood stage development. To identify pathways essential for parasite transmission between their mammalian host and mosquito vector, we undertook a systematic functional analysis of ePKs in the genetically tractable rodent parasite Plasmodium berghei. Modeling domain signatures of conventional ePKs identified 66 putative Plasmodium ePKs. Kinomes are highly conserved between Plasmodium species. Using reverse genetics, we show that 23 ePKs are redundant for asexual erythrocytic parasite development in mice. Phenotyping mutants at four life cycle stages in Anopheles stephensi mosquitoes revealed functional clusters of kinases required for sexual development and sporogony. Roles for a putative SR protein kinase (SRPK) in microgamete formation, a conserved regulator of clathrin uncoating (GAK) in ookinete formation, and a likely regulator of energy metabolism (SNF1/KIN) in sporozoite development were identified.

Place, publisher, year, edition, pages
Elsevier, 2010. Vol. 8, no 4, p. 377-387
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Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-165874DOI: 10.1016/j.chom.2010.09.006ISI: 000283806000010PubMedID: 20951971OAI: oai:DiVA.org:umu-165874DiVA, id: diva2:1379120
Funder
Wellcome trust, WT078335MAWellcome trust, WT089085/Z/09/ZAvailable from: 2019-12-16 Created: 2019-12-16 Last updated: 2019-12-18Bibliographically approved

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