Protein kinase PfPK2 mediated signalling is critical for host erythrocyte invasion by malaria parasite

Signalling pathways in malaria parasite remain poorly defined and major reason for this is the lack of understanding of the function of majority of parasite protein kinases and phosphatases in parasite signalling and its biology. In the present study, we have elucidated the function of Protein Kinase 2 (PfPK2), which is known to be indispensable for the survival of human malaria parasite Plasmodium falciparum. We demonstrate that it is involved in the invasion of host erythrocytes, which is critical for establishing infection. In addition, PfPK2 may also be involved in the maturation of the parasite post-invasion. PfPK2 regulates the release of microneme proteins like Apical Membrane Antigen 1 (AMA1), which facilitates the formation of Tight Junction between the merozoite and host erythrocyte- a key step in the process of invasion. Comparative phosphoproteomics studies revealed that PfPK2 may be involved in regulation of several key proteins involved in invasion and signalling. Furthermore, PfPK2 regulates the generation of cGMP and the release of calcium in the parasite, which are key second messengers for the process of invasion. These and other studies have shed light on a novel signalling pathway in which PfPK2 acts as an upstream regulator of important cGMP-calcium signalling, which plays an important role in parasite invasion. Protein kinases, the enzymes involved in phosphorylation of proteins, are critical mediators of cellular signalling. We have unravelled a novel signalling pathway involving protein kinase PfPK2 in human malaria parasite. PfPK2 is indispensable for the parasite development and in the present study we demonstrate that PfPK2 regulates the process of host erythrocyte invasion by the malaria parasite, which is critical for establishing the infection in the host. PfPK2 may regulate this process by targeting proteins involved in signalling and in turn regulate levels of cGMP and calcium levels, which are known to be critical for invasion. In addition to providing insights into novel mechanisms involved in parasite invasion, these studies also highlight the possibility of targeting PfPK2 signalling pathway for blocking malarial infection.