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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 Kinas...

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Autores principales: Rawat, Rahul Singh, Gupta, Ankit, Antil, Neelam, Bhatnagar, Sonika, Singh, Monika, Rawat, Akanksha, Prasad, T. S. Keshava, Sharma, Pushkar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10662742/
https://www.ncbi.nlm.nih.gov/pubmed/37988347
http://dx.doi.org/10.1371/journal.ppat.1011770
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author Rawat, Rahul Singh
Gupta, Ankit
Antil, Neelam
Bhatnagar, Sonika
Singh, Monika
Rawat, Akanksha
Prasad, T. S. Keshava
Sharma, Pushkar
author_facet Rawat, Rahul Singh
Gupta, Ankit
Antil, Neelam
Bhatnagar, Sonika
Singh, Monika
Rawat, Akanksha
Prasad, T. S. Keshava
Sharma, Pushkar
author_sort Rawat, Rahul Singh
collection PubMed
description 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.
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spelling pubmed-106627422023-11-21 Protein kinase PfPK2 mediated signalling is critical for host erythrocyte invasion by malaria parasite Rawat, Rahul Singh Gupta, Ankit Antil, Neelam Bhatnagar, Sonika Singh, Monika Rawat, Akanksha Prasad, T. S. Keshava Sharma, Pushkar PLoS Pathog Research Article 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. Public Library of Science 2023-11-21 /pmc/articles/PMC10662742/ /pubmed/37988347 http://dx.doi.org/10.1371/journal.ppat.1011770 Text en © 2023 Rawat et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Rawat, Rahul Singh
Gupta, Ankit
Antil, Neelam
Bhatnagar, Sonika
Singh, Monika
Rawat, Akanksha
Prasad, T. S. Keshava
Sharma, Pushkar
Protein kinase PfPK2 mediated signalling is critical for host erythrocyte invasion by malaria parasite
title Protein kinase PfPK2 mediated signalling is critical for host erythrocyte invasion by malaria parasite
title_full Protein kinase PfPK2 mediated signalling is critical for host erythrocyte invasion by malaria parasite
title_fullStr Protein kinase PfPK2 mediated signalling is critical for host erythrocyte invasion by malaria parasite
title_full_unstemmed Protein kinase PfPK2 mediated signalling is critical for host erythrocyte invasion by malaria parasite
title_short Protein kinase PfPK2 mediated signalling is critical for host erythrocyte invasion by malaria parasite
title_sort protein kinase pfpk2 mediated signalling is critical for host erythrocyte invasion by malaria parasite
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10662742/
https://www.ncbi.nlm.nih.gov/pubmed/37988347
http://dx.doi.org/10.1371/journal.ppat.1011770
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