Identification of a casein kinase II phosphorylation domain in NS1 protein of H5N1 influenza virus

Anwar, Tamanna; Khan, Asad

doi:10.6026/97320630002057

Cited by 4 publications

(3 citation statements)

References 23 publications

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“…Changes like that are known to change secondary structure, altering solvent exposure and interactions between proteins. [48][49][50] However, no mutation seemed to induce conformational alterations in the third cytoplasmic loop. The coil structure was maintained in all rare variants.…”

Section: Discussionmentioning

confidence: 99%

Is there a role for rare variants in DRD4 gene in the susceptibility for ADHD? Searching for an effect of allelic heterogeneity

et al. 2011

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Although several studies have demonstrated an association between the 7-repeat (7R) allele in the 48-bp variable number of tandem repeats (VNTRs) in the exon 3 at dopamine receptor D4 (DRD4) gene and attention-deficit/hyperactivity disorder (ADHD), others failed to replicate this finding. In this study, a total of 786 individuals with ADHD were genotyped for DRD4 exon 3 VNTR. All 7R homozygous subjects were selected for VNTR re-sequencing. Subjects homozygous for the 4R allele were selected paired by age, ancestry and disorder subtypes in order to have a sample as homogeneous as possible with 7R/7R individuals. Using these criteria, 103 individuals (66 with ADHD and 37 control individuals) were further investigated. An excess of rare variants were observed in the 7R alleles of ADHD patient when compared with controls (P=0.031). This difference was not observed in 4R allele. Furthermore, nucleotide changes that predict synonymous and non-synonymous substitutions were more common in the 7R sample (P=0.008 for total substitutions and P=0.043 for non-synonymous substitutions). In silico prediction of structural/functional alterations caused by these variants have also been observed. Our findings suggest that not only repeat length but also DNA sequence should be assessed to better understand the role of DRD4 exon 3 VNTR in ADHD genetic susceptibility.

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Section: Discussionmentioning

confidence: 99%

Is there a role for rare variants in DRD4 gene in the susceptibility for ADHD? Searching for an effect of allelic heterogeneity

et al. 2011

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“…NS1 and the RNP components including NP are phosphoproteins in various types and strains of influenza viruses (Sanz-Ezquerro et al, 1998;Bui et al, 2002;Arrese & Portela, 1996;Skorko et al, 1991;Marschall et al, 1999;Neumann et al, 1997;Privalsky & Penhoet, 1978, 1981. Several cellular protein kinases, including protein kinase C (PKC), casein kinase II, cyclin-dependent kinases (CDKs) and extracellular signal-regulated kinases (ERKs) were described as candidates for catalysing one or more of these important protein modifications (Anwar & Khan, 2007;Hale et al, 2008b;Neumann et al, 1997). PKC inhibitors were found to exert a block of influenza virus replication, mainly directed to viral entry (Sieczkarski et al, 2003;Root et al, 2000).…”

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confidence: 99%

Influenza A virus proteins PB1 and NS1 are subject to functionally important phosphorylation by protein kinase C

Mahmoudian

Auerochs

Gröne

et al. 2009

Journal of General Virology

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The virulence of influenza A viruses depends on the activity of the viral RNA polymerase complex and viral regulatory phosphoproteins. We identified that the protein kinase C (PKC) inhibitor Gö 6976 had a post-entry anti-influenza viral effect, by using a polymerase activity-based reporter assay. This inhibitory effect was observed for influenza virus-infected cells as well as for cells transiently transfected with constructs for the RNA polymerase complex. Importantly, the in vitro analysis of viral protein phosphorylation identified PKCa as a kinase phosphorylating PB1 and NS1, but not PB2, PA or NP. Gö 6976 was able to block PKC-specific phosphorylation in vitro. Thus, our data suggest that PKC contributes to the phosphorylation of influenza PB1 and NS1 proteins which appears to be functionally relevant for both viral RNA polymerase activity and efficient viral replication.Influenza A viruses are pathogens that cause significant morbidity and mortality in humans and a variety of animal species (Palese & Shaw, 2007;Wright et al., 2007). Influenza viruses possess a segmented negative-sense RNA genome which is replicated in the nucleus of infected cells. The virulence of individual virus strains is based on a complex co-action of determinants, including the viral haemagglutinin (HA), the RNA-dependent RNA polymerase (subunits PB1, PB2 and PA) and the nonstructural protein (NS1) (Geiss et al., 2002;Tumpey et al., 2005Tumpey et al., , 2007. The RNA-dependent RNA polymerase complex is responsible for both transcription and genomic replication (Torreira et al., 2007;Palese & Shaw, 2007). PB1 represents the central catalytic subunit of the polymerase complex (Honda & Ishihama, 1997;Poch et al., 1989;Torreira et al., 2007), PB2 is responsible for recognition and binding of the cap structures of host mRNAs which are used for priming viral transcription (Fechter & Brownlee, 2005;Guilligay et al., 2008), while PA combines essential activities required for genome replication and protein processing (Fodor & Smith, 2004;Maier et al., 2008;Palese & Shaw, 2007). The viral nucleoprotein (NP) strictly associates with the RNA polymerase complex to form viral ribonucleoproteins (RNPs) (Noda et al., 2006;Portela & Digard, 2002), it stimulates RNA polymerase activity and mediates nuclear RNP translocation (Neumann et al., 1997;Bui et al., 2002;Portela & Digard, 2002). The viral regulatory protein NS1 provides a number of functions required for efficient replication and gene expression (Hale et al., 2008a). An interaction between NS1 and the viral transcription-replication complex was reported (Marion et al., 1997) but awaits a confirmation in functional aspects. NS1 and the RNP components including NP are phosphoproteins in various types and strains of influenza viruses (Sanz-Ezquerro et al., 1998;Bui et al., 2002;Arrese & Portela, 1996;Skorko et al., 1991;Marschall et al., 1999;Neumann et al., 1997;Privalsky & Penhoet, 1978, 1981. Several cellular protein kinases, including protein kinase C (PKC), casein kinase II, cyclin-dependen...

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“…7 of the potential phosphorylation sites are Casein kinase II (CKII) phosphorylation sites encompassing different region of the protein. One study has previously reported a CKII phosphorylation domain [ 10 ]. 16 of the potential phosphorylation sites are Protein kinase C (PKC) phosphorylation site encompassing different regions of the protein.…”

Section: Resultsmentioning

confidence: 99%

Correlating novel variable and conserved motifs in the Hemagglutinin protein with significant biological functions

Gendoo

ElHefnawi

Werner

et al. 2008

Virol J

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Background: Variations in the influenza Hemagglutinin protein contributes to antigenic drift resulting in decreased efficiency of seasonal influenza vaccines and escape from host immune response. We performed an in silico study to determine characteristics of novel variable and conserved motifs in the Hemagglutinin protein from previously reported H3N2 strains isolated from Hong Kong from 1968-1999 to predict viral motifs involved in significant biological functions.

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Identification of a casein kinase II phosphorylation domain in NS1 protein of H5N1 influenza virus

Cited by 4 publications

References 23 publications

Is there a role for rare variants in DRD4 gene in the susceptibility for ADHD? Searching for an effect of allelic heterogeneity

Is there a role for rare variants in DRD4 gene in the susceptibility for ADHD? Searching for an effect of allelic heterogeneity

Influenza A virus proteins PB1 and NS1 are subject to functionally important phosphorylation by protein kinase C

Correlating novel variable and conserved motifs in the Hemagglutinin protein with significant biological functions

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