Cell Signaling through the Protein Kinases cAMP-dependent Protein Kinase, Protein Kinase Cϵ, and RAF-1 Regulates Amphotropic Murine Leukemia Virus Envelope Protein-induced Syncytium Formation

Wang, Wei; Jobbágy, Zsolt; Bird, Terry H.; Eiden, Maribeth V.; Anderson, Wayne B.

doi:10.1074/jbc.m411537200

Cited by 7 publications

(5 citation statements)

References 55 publications

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“…The HIV-1 JR CSF Env gene expression construct pCMV/ R-Env was described previously (25). pCI4070A, encoding the amphotropic murine leukemia virus (A-MLV) envelope protein, was described previously (26). A vesicular stomatitis virus glycoprotein (VSV G) gene expression construct (27) was provided by Theodore Friedmann (University of California at San Diego, La Jolla, CA).…”

Section: Methodsmentioning

confidence: 99%

Influenza Virus M2 Protein Ion Channel Activity Helps To Maintain Pandemic 2009 H1N1 Virus Hemagglutinin Fusion Competence during Transport to the Cell Surface

Alvarado-Facundo

Gao

Ribas‐Aparicio

et al. 2015

J Virol

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The influenza virus hemagglutinin (HA) envelope protein mediates virus entry by first binding to cell surface receptors and then fusing viral and endosomal membranes during endocytosis. Cleavage of the HA precursor (HA0) into a surface receptor-binding subunit (HA1) and a fusion-inducing transmembrane subunit (HA2) by host cell enzymes primes HA for fusion competence by repositioning the fusion peptide to the newly created N terminus of HA2. We previously reported that the influenza virus M2 protein enhances pandemic 2009 influenza A virus [(H1N1)pdm09] HA-pseudovirus infectivity, but the mechanism was unclear. In this study, using cell-cell fusion and HA-pseudovirus infectivity assays, we found that the ion channel function of M2 was required for enhancement of HA fusion and HA-pseudovirus infectivity. The M2 activity was needed only during HA biosynthesis, and proteolysis experiments indicated that M2 proton channel activity helped to protect (H1N1)pdm09 HA from premature conformational changes as it traversed low-pH compartments during transport to the cell surface. While M2 has previously been shown to protect avian influenza virus HA proteins of the H5 and H7 subtypes that have polybasic cleavage motifs, this study demonstrates that M2 can protect HA proteins from human H1N1 strains that lack a polybasic cleavage motif. This finding suggests that M2 proton channel activity may play a wider role in preserving HA fusion competence among a variety of HA subtypes, including HA proteins from emerging strains that may have reduced HA stability. IMPORTANCEInfluenza virus infects cells when the hemagglutinin (HA) surface protein undergoes irreversible pH-induced conformational changes after the virus is taken into the cell by endocytosis. HA fusion competence is primed when host cell enzymes cleave the HA precursor. The proton channel function of influenza virus M2 protein has previously been shown to protect avian influenza virus HA proteins that contain a polybasic cleavage site from pH-induced conformational changes during biosynthesis, but this effect is less well understood for human influenza virus HA proteins that lack polybasic cleavage sites. Using assays that focus on HA entry and fusion, we found that the M2 protein also protects (H1N1)pdm09 influenza A virus HA from premature conformational changes as it transits low-pH compartments during biosynthesis. This work suggests that M2 may play a wider role in preserving HA function in a variety of influenza virus subtypes that infect humans and may be especially important for HA proteins that are less stable. T he influenza virus hemagglutinin (HA) envelope protein mediates virus entry by binding to cell surface receptors, followed by endocytosis and fusion of the viral and endosomal membranes. Cellular proteases cleave the HA precursor (HA0) to generate the HA1 surface subunit, which mediates binding to cell surface sialic acid receptors, and the HA2 transmembrane subunit, which mediates membrane fusion between viral and endosomal membranes during e...

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Section: Methodsmentioning

confidence: 99%

Influenza Virus M2 Protein Ion Channel Activity Helps To Maintain Pandemic 2009 H1N1 Virus Hemagglutinin Fusion Competence during Transport to the Cell Surface

Alvarado-Facundo

Gao

Ribas‐Aparicio

et al. 2015

J Virol

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“…It has been suggested that virus-cell surface receptor interactions can elicit two types of signals, i.e., conformational changes of viral particles and concomitant intracellular signals triggering specific cellular reactions (19). Indeed, cellular signal transduction pathways and associated protein kinases are implicated in retrovirus-induced cell-cell fusion (56). For instance, HIV-1 envelope interacts with the CCR5 coreceptor and activates the G␣ q pathway to trigger HIV-1-induced cellcell fusion (20).…”

mentioning

confidence: 99%

Reciprocal Regulation of AKT and MAP Kinase Dictates Virus-Host Cell Fusion

Sharma

Mani

Nandwani

et al. 2010

J Virol

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“…We further measured changes in silkworm BR-C phosphorylation after treatments with specific activators and inhibitors of PKA in vitro and ex vivo. Using previously reported protocols (16,17), we treated the silkworm BmE cells overexpressing BR-C with two PKA activators, namely, cAMP and forskolin, and two inhibitors, namely, H89 and KT5720, and then BR-C phosphorylation levels were examined by Western blot assays with the p-BR-C antibody against the Ser-186 site. Compared with a control treated by dimethyl sulfoxide (DMSO), the phosphorylation levels of BR-C were increased Ͼ2-fold after PKA activator (cAMP or forskolin) treatment (Fig.…”

Section: Pka Mediated Br-c Phosphorylation At Ser-186mentioning

confidence: 99%

Protein kinase A-mediated phosphorylation of the Broad-Complex transcription factor in silkworm suppresses its transcriptional activity

Qian

Gang

Zhang

et al. 2017

Journal of Biological Chemistry

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The insect-specific transcription factor Broad-Complex (BR-C) is transcriptionally activated by the steroid 20-hydroxyecdysone (20E) and regulates the expression of many target genes involved in insect growth and development. However, although the transcriptional regulation of BR-C proteins has been well studied, how BR-C is regulated at post-transcription and -translation levels is poorly understood. To this end, using liquid chromatography-tandem mass spectrometry analysis, we identified residue Ser-186 as a phosphorylation site of BR-C in silkworm. Site-directed mutagenesis and treatment with specific kinase activators and inhibitors indicated that the Ser-186 residue in silkworm BR-C is phosphorylated by protein kinase A (PKA). Immunostaining assays disclosed that PKA-mediated phosphorylation of silkworm BR-C has no effect on its nuclear import. However, luciferase reporter analysis, electrophoretic mobility shift assays, and chromatin immunoprecipitation revealed that the PKA phosphorylation event suppresses the transcriptional activation of silkworm BR-C target genes and that this inhibition was caused by repression of BR-C binding to its DNA targets. Of note, both and experiments disclosed that a continuous 20E signal inhibits the PKA-mediated BR-C phosphorylation and also the cAMP/PKA pathway, indicating that 20E's inhibitory effect on PKA-mediated phosphorylation of silkworm BR-C contributes to maintaining BR-C transcriptional activity. In conclusion, our findings indicate that PKA-mediated phosphorylation inhibits silkworm BR-C activity by interfering with its binding to DNA and that 20E signaling relieves PKA-mediated phosphorylation of BR-C, thereby maintaining its transcriptional activity.

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Cell Signaling through the Protein Kinases cAMP-dependent Protein Kinase, Protein Kinase Cϵ, and RAF-1 Regulates Amphotropic Murine Leukemia Virus Envelope Protein-induced Syncytium Formation

Abstract: Amphotropic murine leukemia virus (A-MuLV

Cited by 7 publications

References 55 publications

Influenza Virus M2 Protein Ion Channel Activity Helps To Maintain Pandemic 2009 H1N1 Virus Hemagglutinin Fusion Competence during Transport to the Cell Surface

Influenza Virus M2 Protein Ion Channel Activity Helps To Maintain Pandemic 2009 H1N1 Virus Hemagglutinin Fusion Competence during Transport to the Cell Surface

Reciprocal Regulation of AKT and MAP Kinase Dictates Virus-Host Cell Fusion

Protein kinase A-mediated phosphorylation of the Broad-Complex transcription factor in silkworm suppresses its transcriptional activity

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