Protein kinase A activity is associated with metacyclogenesis in <i>Leishmania amazonensis</i>

Genestra, Marcelo; Cysne-Finkelstein, Léa; Leon, Leonor L.

doi:10.1002/cbf.1107

Cited by 21 publications

(12 citation statements)

References 42 publications

(30 reference statements)

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“…Conditions inducing differentiation of the L. donovani promastigote to the amastigote stage cause a three-to fourfold elevation in cAMP levels and cAMP-dependent kinase activity [57]. In L. amazonensis, PKA has been suggested to play a role in metacyclogenesis, since cAMP-dependent kinase activity peaked in promastigotes with a high concentration of metacyclics [58]. An impact of PKA on Leishmania infectivity has also been proposed by the use of PKA-specific inhibitors and activators in L. major [45].…”

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confidence: 99%

Kinetoplastid AGC Kinases

Bachmaier

Boshart

2013

Protein Phosphorylation in Parasites

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Genes encoding protein kinases homologous to the AGC (PKA-PKG-PKC-like) group are relatively under-represented in trypanosomatid genomes, and most of them cannot be assigned to one of the subfamilies conserved in higher organisms, as illustrated by the zinc finger kinase ZFK, a kinase with unique and kinetoplastid-specific domain architecture outside the catalytic core. Second messenger-regulated kinases are apparently absent, like the PKC and PKG subfamilies, or have controversial ligand-binding properties, like PKA. Hence, the AGC group is very unconventional in kinetoplastids. Only the nuclear DBF2-related (NDR) kinases PK50 and PK53 are currently being prioritized for drug development. In this chapter the currently available knowledge on AGC kinases is reviewed, and the suggestion made that further investigations of this group of kinases will most likely deliver parasite-specific kinase drug targets.

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confidence: 99%

Kinetoplastid AGC Kinases

Bachmaier

Boshart

2013

Protein Phosphorylation in Parasites

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“…PKA activity assay in the presence and absence of cAMP and cGMP analogs and PKA inhibitors in both soluble fraction (SF) and membrane fraction (MF) of infective promastigotes of L. amazonensis showed increase in phosphorylative activity of the kinase in cAMP-analog-treated cells, and not in cGMP-analog-treated cells, was conspicuous, particularly in the SF of the promastigotes. On the contrary, PKA activity of both SF and MF of axenic amastigotes was found to be much lower as compared to that of both SF and MF of infective promastigotes under same experimental conditions [66].…”

Section: Pka As the Downstream Effector Of Camp In Leishmaniamentioning

confidence: 68%

Role of cAMP Homeostasis in Intra-Macrophage Survival and Infectivity of Unicellular Parasites likeLeishmania

Biswas¹,

Bhattacharjee²,

Das³

2020

Vector-Borne Diseases - Recent Developments in Epidemiology and Control

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Unicellular eukaryotic pathogen Leishmania donovani, an intra-macrophage protozoan parasite, on exposure to phagolysosome conditions (PC) of mammalian macrophages, show increased cAMP level and cAMP-dependent protein kinase A (PKA) resulting in resistance to macrophage oxidative burst. In order to have a comprehensive understanding of cAMP signaling and their contribution to infectivity, studies were carried out on all the enzymes associated with cAMP metabolism such as adenylate cyclase, phosphodiesterase, pyrophosphatase and the regulatory and catalytic subunits of PKA. This chapter deals in detail the contribution of these components of cAMP signaling in cAMP homeostasis of the parasite as well as their role on successful host-parasite interaction leading to intracellular parasite survival and establishment of infection. Finally, a discussion is made about how these observations might be exploited for developing drug candidates targeting parasite specific features.

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“…However, unlike higher eukaryotes, very little is known about the role of PKA in Leishmania. In 2004, PKA activity was found to be higher in metacyclic forms compared to non-infective forms, which may suggest the involvement of the enzyme in the process of parasite metacyclogenesis [108].…”

Section: Leishmaniamentioning

confidence: 95%

Intracellular Signaling Pathways Involved in Cell Differentiation in Trypanosomatids

Lopes

Gomes²,

Dutra³

et al. 2010

TOPARAJ

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Knowledge of cell signaling pathways in trypanosomatids is crucial for the future design of new drugs to treat diseases caused by these parasites. The publication of the complete genome sequences of three pathogenic trypanosomatids, Trypanosoma brucei, T. cruzi and Leishmania major, revealed numerous protein members of signaling pathways that modulate important processes, such as cell differentiation. Even so, little is known about the role that these proteins play in the physiology of trypanosomatids. This review aims to stimulate discussion on this subject to encourage further studies of the signaling pathways involved in the cell differentiation of trypanosomatids.

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Protein kinase A activity is associated with metacyclogenesis in Leishmania amazonensis

Cited by 21 publications

References 42 publications

Kinetoplastid AGC Kinases

Kinetoplastid AGC Kinases

Role of cAMP Homeostasis in Intra-Macrophage Survival and Infectivity of Unicellular Parasites likeLeishmania

Intracellular Signaling Pathways Involved in Cell Differentiation in Trypanosomatids

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