A secreted Plasmodium falciparum kinase reveals a signature motif for classification of tyrosine kinase-like kinases

Thorough bioinformatic and phylogenetic analyses of Plasmodium falciparum tyrosine kinase-like kinase (TKL) sequences revealed a clear evolutionary relationship of PF3D7_1121300 (thereafter called PfTKL2) to the IL-1 receptor-associated kinase (IRAK)/receptor-like kinase (RLK)/Pelle protein family. We identified a novel conserved motif that is unique to this family, as well as an insertion whose length allows distribution of its members into two distinct subfamilies, in a way that matches exactly the dichotomy between Tube/Tube-like kinases (TTLKs) and Pelle-like kinases (PLKs) distinguished previously on the basis of features in accessory domains. The PfTKL2 protein is expressed ubiquitously in asexual blood stages and in gametocytes, and the recombinant enzyme displays kinase activity in vitro. The protein is exported to the host erythrocyte; furthermore, in accordance with data from a previous study of the extracellular proteome of Plasmodium-infected erythrocytes, we show that PfTKL2 is secreted into the culture medium. Considering the functions of other members of the RLK/Pelle family in immunity, and its secretion to the extracellular medium, we speculate that PfTKL2 functions may include an immunomodulatory role promoting parasite survival in the human host.