scholarly journals Inhibition of RNase L and RNA-dependent Protein Kinase (PKR) by Sunitinib Impairs Antiviral Innate Immunity

2011 ◽  
Vol 286 (30) ◽  
pp. 26319-26326 ◽  
Author(s):  
Babal Kant Jha ◽  
Irina Polyakova ◽  
Patricia Kessler ◽  
Beihua Dong ◽  
Benjamin Dickerman ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Protein Kinase ◽  
Rnase L ◽  
Dependent Protein Kinase ◽  
Dependent Protein ◽  
Antiviral Innate Immunity

scholarly journals Stress Granules Regulate Double-Stranded RNA-Dependent Protein Kinase Activation through a Complex Containing G3BP1 and Caprin1

mBio ◽  
2015 ◽  
Vol 6 (2) ◽  
Author(s):  
Lucas C. Reineke ◽  
Nancy Kedersha ◽  
Martijn A. Langereis ◽  
Frank J. M. van Kuppeveld ◽  
Richard E. Lloyd
Keyword(s):  
Pattern Recognition ◽  
Innate Immunity ◽  
Protein Kinase ◽  
Antiviral Activity ◽  
Stress Granules ◽  
Initiation Factor ◽  
Dependent Protein Kinase ◽  
Α Subunit ◽  
Double Stranded Rna ◽  
Dependent Protein

ABSTRACT Stress granules (SGs) are dynamic cytoplasmic repositories containing translationally silenced mRNAs that assemble upon cellular stress. We recently reported that the SG nucleating protein G3BP1 promotes antiviral activity and is essential in double-stranded RNA-dependent protein kinase (PKR) recruitment to stress granules, thereby driving phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α). Here, we delineate the mechanism for SG-dependent PKR activation. We show that G3BP1 and inactive PKR directly interact with each other, dependent on both the NTF2-like and PXXP domains of G3BP1. The G3BP1-interacting protein Caprin1 also directly interacts with PKR, regulates efficient PKR activation at the stress granule, and is also integral for the release of active PKR into the cytoplasm to engage in substrate recognition. The G3BP1-Caprin1-PKR complex represents a new mode of PKR activation and is important for antiviral activity of G3BP1 and PKR during infection with mengovirus. Our data links stress responses and their resultant SGs with innate immune activation through PKR without a requirement for foreign double-stranded RNA (dsRNA) pattern recognition. IMPORTANCE Our previous work indicates that stress granules have antiviral activity and mediate innate immunity through functions of G3BP1; however, the mechanistic details of these functions were not resolved. We show that much of the antiviral activity of stress granules is contingent on the function of PKR in a complex with G3BP1 and Caprin1. The PKR-G3BP1-Caprin1 complex undergoes dynamic transitioning within and outside stress granules to accomplish PKR activation and translational repression. This mechanism appears to function distinctly from canonical pattern recognition of double-stranded RNA by PKR. Therefore, this mechanism bridges the stress response with innate immunity, allowing the cell to respond to many cellular stressors and amplify the pathogen pattern recognition systems of innate immunity.

scholarly journals Essential Role for the dsRNA-Dependent Protein Kinase PKR in Innate Immunity to Viral Infection

Immunity ◽  
2000 ◽  
Vol 13 (1) ◽  
pp. 129-141 ◽  
Author(s):  
Siddharth Balachandran ◽  
Paul C Roberts ◽  
Laura E Brown ◽  
Ha Truong ◽  
Asit K Pattnaik ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Protein Kinase ◽  
Viral Infection ◽  
Essential Role ◽  
Dependent Protein Kinase ◽  
Dependent Protein

scholarly journals RNase L and Double-Stranded RNA-Dependent Protein Kinase Exert Complementary Roles in Islet Cell Defense during Coxsackievirus Infection

2005 ◽  
Vol 174 (3) ◽  
pp. 1171-1177 ◽  
Author(s):  
Malin Flodström-Tullberg ◽  
Monica Hultcrantz ◽  
Alexandr Stotland ◽  
Amy Maday ◽  
Devin Tsai ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Islet Cell ◽  
Rnase L ◽  
Dependent Protein Kinase ◽  
Double Stranded Rna ◽  
Cell Defense ◽  
Dependent Protein

CS09-5. DNA-dependent protein kinase is a DNA sensor for IRF-3-dependent innate immunity

Cytokine ◽  
2011 ◽  
Vol 56 (1) ◽  
pp. 57
Author(s):  
Brian Ferguson ◽  
Daniel Mansur ◽  
Nicholas Peters ◽  
Geoffrey Smith
Keyword(s):  
Innate Immunity ◽  
Protein Kinase ◽  
Dna Sensor ◽  
Dependent Protein Kinase ◽  
Dependent Protein

scholarly journals RNase L Mediates Transient Control of the Interferon Response through Modulation of the Double-stranded RNA-dependent Protein Kinase PKR

2003 ◽  
Vol 278 (22) ◽  
pp. 20124-20132 ◽  
Author(s):  
Khalid S. A. Khabar ◽  
Yunus M. Siddiqui ◽  
Fahad Al-Zoghaibi ◽  
Latifa Al-Haj ◽  
Mohammed Dhalla ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Interferon Response ◽  
Rnase L ◽  
Dependent Protein Kinase ◽  
Double Stranded Rna ◽  
Transient Control ◽  
Dependent Protein
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