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Transgenic Analysis of the MAP Kinase MPK10 Reveals an Auto-inhibitory Mechanism Crucial for Stage-Regulated Activity and Parasite Viability


Leishmaniasis is an important human disease caused by Leishmania parasites. A crucial aspect of Leishmania infectivity is its capacity to sense different environments and adapt for survival inside insect vector and vertebrate host by stage differentiation. This process is triggered by environmental changes encountered in these organisms, including temperature and pH shifts, which usually are sensed and transduced by signaling cascades including protein kinases and their substrates. In this study, we analyzed the regulation of the Leishmania mitogen-activated protein kinase MPK10 using protein purified from transgenic parasites and combining site-directed mutagenesis and activity tests. We demonstrate that this kinase is activated during parasite differentiation and regulated by an atypical mechanism involving auto-inhibition, which is essential for parasite viability.


Vyšlo v časopise: Transgenic Analysis of the MAP Kinase MPK10 Reveals an Auto-inhibitory Mechanism Crucial for Stage-Regulated Activity and Parasite Viability. PLoS Pathog 10(9): e32767. doi:10.1371/journal.ppat.1004347
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004347

Souhrn

Leishmaniasis is an important human disease caused by Leishmania parasites. A crucial aspect of Leishmania infectivity is its capacity to sense different environments and adapt for survival inside insect vector and vertebrate host by stage differentiation. This process is triggered by environmental changes encountered in these organisms, including temperature and pH shifts, which usually are sensed and transduced by signaling cascades including protein kinases and their substrates. In this study, we analyzed the regulation of the Leishmania mitogen-activated protein kinase MPK10 using protein purified from transgenic parasites and combining site-directed mutagenesis and activity tests. We demonstrate that this kinase is activated during parasite differentiation and regulated by an atypical mechanism involving auto-inhibition, which is essential for parasite viability.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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