The Role of Tyrosine Phosphorylation of Protein Kinase C Delta in Infection and Inflammation

Yang, Qingliang; Langston, Jordan C.; Tang, Yuan; Kiani, Mohammad F.; Kilpatrick, Laurie E.

doi:10.3390/ijms20061498

Cited by 41 publications

(40 citation statements)

References 131 publications

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“…In addition, neutrophil adhesion, which is crucial to migration, was enhanced by LPS stimulation. During sepsis, increasing the adhesion of neutrophils leads to enhanced interactions between neutrophils and endothelial cells followed by vascular endothelial injury and organ dysfunction (26). Our results demonstrated that AMP treatment reduced adhesion and that this effect was A1R-dependent.…”

Section: Discussionsupporting

confidence: 51%

Extracellular AMP Suppresses Endotoxemia-Induced Inflammation by Alleviating Neutrophil Activation

et al. 2020

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Intracellular adenosine monophosphate (AMP) is indispensable for cellular metabolic processes, and it is interconverted to ADP and/or ATP or activates AMP-activated protein kinase (AMPK). However, the specific biological function of extracellular AMP has not been identified. We evaluated the effect of extracellular AMP using in vivo and in vitro models of endotoxemia. We found that AMP inhibited inflammation and neutrophil activation in lipopolysaccharide (LPS)-induced endotoxemic mice. The effects of extracellular AMP were abolished by an adenosine 1 receptor (A1R) antagonist but were not influenced by inhibiting the conversion of AMP to adenosine (ADO), indicating that AMP inhibited inflammation by directly activating A1R. In addition, in vitro experiments using LPS-stimulated mouse neutrophils showed that AMP inhibited LPS-induced reactive oxygen species (ROS) production, degranulation, and cytokine production, while the effects were reversed by an A1R antagonist. Further research showed that AMP regulated LPS-stimulated neutrophil functions by inhibiting the p38 MAPK pathway. These findings were also confirmed in primary neutrophils derived from healthy human blood. Moreover, we collected serum samples from septic patients. We found that AMP levels were increased compared with those of healthy volunteers and that AMP levels were negatively correlated with disease severity. Together, these data provide evidence that extracellular AMP acts on A1R to suppress endotoxemia-induced inflammation by inhibiting neutrophil overactivation and that the p38 MAPK signaling pathway is involved.

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Section: Discussionsupporting

confidence: 51%

Extracellular AMP Suppresses Endotoxemia-Induced Inflammation by Alleviating Neutrophil Activation

et al. 2020

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“…PKCδ localizes to multiple subcellular sites including the plasma membrane, cytoplasm, and nucleus, with localization impacted by its activation status [ 29 ]. PKCδ acquires activating phosphorylation marks during influenza virus infection [ 27 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

Phosphorylation controls RNA binding and transcription by the influenza virus polymerase

et al. 2020

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The influenza virus polymerase transcribes and replicates the viral genome. The proper timing and balance of polymerase activity is important for successful replication. Genome replication is controlled in part by phosphorylation of NP that regulates assembly of the replication machinery. However, it remains unclear whether phosphorylation directly regulated polymerase activity. Here we identified polymerase phosphosites that control its function. Mutating phosphosites in the catalytic subunit PB1 altered polymerase activity and virus replication. Biochemical analyses revealed phosphorylation events that disrupted global polymerase function by blocking the NTP entry channel or preventing RNA binding. We also identified a regulatory site that split polymerase function by specifically suppressing transcription. These experiments show that host kinases phospho-regulate viral RNA synthesis directly by modulating polymerase activity and indirectly by controlling assembly of replication machinery. Further, they suggest polymerase phosphorylation may bias replication versus transcription at discrete times or locations during the infectious cycle.

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“…To effectively respond to environmental antigens, the immune system is exquisitely balanced 63 . PTMs, such as phosphorylation, help to ensure the balance of immune signal transduction by activating or terminating the immune responses at the proper time 64 . In our study, GO analysis showed that 183 phosphorylated proteins belonging to the ‘immune system process’ term.…”

Section: Discussionmentioning

confidence: 99%

The phosphoproteomic responses of duck (Cairna moschata) to classical/novel duck reovirus infections in the spleen tissue

Yun

Hua

et al. 2020

Sci Rep

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Duck reovirus (DRV) is a fatal member of the genus Orthoreovirus in the family Reoviridae. The disease caused by DRV leads to huge economic losses to the duck industry. Post-translational modification is an efficient strategy to enhance the immune responses to virus infection. However, the roles of protein phosphorylation in the responses of ducklings to Classic/Novel DRV (C/NDRV) infections are largely unknown. Using a high-resolution LC–MS/MS integrated to highly sensitive immune-affinity antibody method, phosphoproteomes of Cairna moschata spleen tissues under the C/NDRV infections were analyzed, producing a total of 8,504 phosphorylation sites on 2,853 proteins. After normalization with proteomic data, 392 sites on 288 proteins and 484 sites on 342 proteins were significantly changed under the C/NDRV infections, respectively. To characterize the differentially phosphorylated proteins (DPPs), a systematic bioinformatics analyses including Gene Ontology annotation, domain annotation, subcellular localization, and Kyoto Encyclopedia of Genes and Genomes pathway annotation were performed. Two important serine protease system-related proteins, coagulation factor X and fibrinogen α-chain, were identified as phosphorylated proteins, suggesting an involvement of blood coagulation under the C/NDRV infections. Furthermore, 16 proteins involving the intracellular signaling pathways of pattern-recognition receptors were identified as phosphorylated proteins. Changes in the phosphorylation levels of MyD88, NF-κB, RIP1, MDA5 and IRF7 suggested a crucial role of protein phosphorylation in host immune responses of C. moschata. Our study provides new insights into the responses of ducklings to the C/NDRV infections at PTM level.

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The Role of Tyrosine Phosphorylation of Protein Kinase C Delta in Infection and Inflammation

Cited by 41 publications

References 131 publications

Extracellular AMP Suppresses Endotoxemia-Induced Inflammation by Alleviating Neutrophil Activation

Extracellular AMP Suppresses Endotoxemia-Induced Inflammation by Alleviating Neutrophil Activation

Phosphorylation controls RNA binding and transcription by the influenza virus polymerase

The phosphoproteomic responses of duck (Cairna moschata) to classical/novel duck reovirus infections in the spleen tissue

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