scholarly journals A divergent kinase lacking the glycine-rich loop regulates membrane ultrastructure of theToxoplasmaparasitophorous vacuole

2018 ◽  
Author(s):  
Tsebaot Beraki ◽  
Hu Xiaoyu ◽  
Malgorzata Broncel ◽  
Joanna C. Young ◽  
William J. O’Shaughnessy ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Parasitophorous Vacuole ◽  
Parasite Infection ◽  
Secreted Proteins ◽  
Membrane Association ◽  
Membrane Biogenesis ◽  
Active Protein ◽  
Apicomplexan Parasites ◽  
Membrane Ultrastructure ◽  
Binding Loop

AbstractApicomplexan parasites replicate within a protective organelle called the parasitophorous vacuole (PV). TheToxoplasma gondiiPV is filled with a network of tubulated membranes, which are thought to facilitate trafficking of effectors and nutrients. Despite being critical to parasite virulence, there is scant mechanistic understanding of the network’s functions. Here, we identify the parasite secreted kinase WNG1 as a critical regulator of tubular membrane biogenesis. WNG1 family members adopt an atypical protein kinase fold lacking the glycine rich ATP-binding loop that is required for catalysis in canonical kinases. Unexpectedly, we find that WNG1 is an active protein kinase that localizes to the PV lumen and phosphorylates PV-resident proteins, several of which are essential for the formation of a functional intravacuolar network. Moreover, we show that WNG1-dependent phosphorylation of these proteins is required for their membrane association, and thus their ability to tubulate membranes. Consequently, WNG1 knockout parasites have an aberrant PV membrane ultrastructure. Collectively, our results describe a unique family ofToxoplasmakinases and implicate phosphorylation of secreted proteins as a mechanism of regulating PV formation during parasite infection.

scholarly journals Divergent kinase regulates membrane ultrastructure of theToxoplasmaparasitophorous vacuole

2019 ◽  
Vol 116 (13) ◽  
pp. 6361-6370 ◽  
Author(s):  
Tsebaot Beraki ◽  
Xiaoyu Hu ◽  
Malgorzata Broncel ◽  
Joanna C. Young ◽  
William J. O’Shaughnessy ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Parasitophorous Vacuole ◽  
Parasite Infection ◽  
Secreted Proteins ◽  
Membrane Association ◽  
Membrane Biogenesis ◽  
Active Protein ◽  
Apicomplexan Parasites ◽  
Membrane Ultrastructure ◽  
Binding Loop

Apicomplexan parasites replicate within a protective organelle, called the parasitophorous vacuole (PV). TheToxoplasma gondiiPV is filled with a network of tubulated membranes, which are thought to facilitate trafficking of effectors and nutrients. Despite being critical to parasite virulence, there is scant mechanistic understanding of the network’s functions. Here, we identify the parasite-secreted kinase WNG1 (With-No-Gly-loop) as a critical regulator of tubular membrane biogenesis. WNG1 family members adopt an atypical protein kinase fold lacking the glycine rich ATP-binding loop that is required for catalysis in canonical kinases. Unexpectedly, we find that WNG1 is an active protein kinase that localizes to the PV lumen and phosphorylates PV-resident proteins, several of which are essential for the formation of a functional intravacuolar network. Moreover, we show that WNG1-dependent phosphorylation of these proteins is required for their membrane association, and thus their ability to tubulate membranes. Consequently, WNG1 knockout parasites have an aberrant PV membrane ultrastructure. Collectively, our results describe a unique family ofToxoplasmakinases and implicate phosphorylation of secreted proteins as a mechanism of regulating PV development during parasite infection.

scholarly journals Frequency- and Afterload-Dependent Cardiac Modulation In Vivo by Troponin I With Constitutively Active Protein Kinase A Phosphorylation Sites

2004 ◽  
Vol 94 (4) ◽  
pp. 496-504 ◽  
Author(s):  
Eiki Takimoto ◽  
David G. Soergel ◽  
Paul M.L. Janssen ◽  
Linda B. Stull ◽  
David A. Kass ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Troponin I ◽  
Phosphorylation Sites ◽  
Active Protein ◽  
Cardiac Modulation ◽  
Kinase A ◽  
Constitutively Active

scholarly journals Coxiella burnetii Alters Cyclic AMP-Dependent Protein Kinase Signaling during Growth in Macrophages

2012 ◽  
Vol 80 (6) ◽  
pp. 1980-1986 ◽  
Author(s):  
Laura J. MacDonald ◽  
Richard C. Kurten ◽  
Daniel E. Voth
Keyword(s):  
Protein Kinase ◽  
Cyclic Amp ◽  
Coxiella Burnetii ◽  
Alveolar Macrophages ◽  
Q Fever ◽  
Parasitophorous Vacuole ◽  
Dependent Protein Kinase ◽  
Content Type ◽  
Bacterial Agent ◽  
Dependent Protein

ABSTRACTCoxiella burnetiiis the bacterial agent of human Q fever, an acute, flu-like illness that can present as chronic endocarditis in immunocompromised individuals. Following aerosol-mediated transmission,C. burnetiireplicates in alveolar macrophages in a unique phagolysosome-like parasitophorous vacuole (PV) required for survival. The mechanisms ofC. burnetiiintracellular survival are poorly defined and a recent Q fever outbreak in the Netherlands emphasizes the need for better understanding this unique host-pathogen interaction. We recently demonstrated that inhibition of host cyclic AMP-dependent protein kinase (PKA) activity negatively impacts PV formation. In the current study, we confirmed PKA involvement in PV biogenesis and probed the role of PKA signaling duringC. burnetiiinfection of macrophages. Using PKA-specific inhibitors, we found the kinase was needed for biogenesis of prototypical PV andC. burnetiireplication. PKA and downstream targets were differentially phosphorylated throughout infection, suggesting prolonged regulation of the pathway. Importantly, the pathogen actively triggered PKA activation, which was also required for PV formation by virulentC. burnetiiisolates during infection of primary human alveolar macrophages. A subset of PKA-specific substrates were differentially phosphorylated duringC. burnetiiinfection, suggesting the pathogen uses PKA signaling to control distinct host cell responses. Collectively, the current results suggest a versatile role for PKA inC. burnetiiinfection and indicate virulent organisms usurp host kinase cascades for efficient intracellular growth.

scholarly journals Constitutively Active Protein Kinase A Qualitatively Mimics the Effects of Follicle-Stimulating Hormone on Granulosa Cell Differentiation

2008 ◽  
Vol 22 (8) ◽  
pp. 1842-1852 ◽  
Author(s):  
Rosalba Escamilla-Hernandez ◽  
Lynda Little-Ihrig ◽  
Kyle E. Orwig ◽  
Junming Yue ◽  
Uma Chandran ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Granulosa Cell ◽  
Follicle Stimulating Hormone ◽  
Active Protein ◽  
Kinase A ◽  
Constitutively Active ◽  
Stimulating Hormone

The bortezomib-induced mitochondrial damage is mediated by accumulation of active protein kinase C-δ

2004 ◽  
Vol 321 (4) ◽  
pp. 905-908 ◽  
Author(s):  
David Durrant ◽  
Jihua Liu ◽  
Hung-Sheng Yang ◽  
Ray M. Lee
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Mitochondrial Damage ◽  
Active Protein ◽  
Kinase C
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