Abstract
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.
► Domain signature modeling identifies 66 putative
Plasmodium
eukaryotic protein kinases ► The complement of protein kinases is largely conserved between
Plasmodium
species ► 23 protein kinase genes are redundant for
P. berghei
asexual erythrocytic development in mice ► 13 mutants reveal essential kinase gene functions in mosquito transmission