Infection of glioma cells with Sindbis virus induces selective activation and tyrosine phosphorylation of protein kinase C delta. Implications for Sindbis virus-induced apoptosis

Sindbis virus (SV) is an alpha virus used as a model for studying the role of apoptosis in virus infection. In this study, we examined the role of protein kinase C (PKC) in the apoptosis induced by SVNI, a virulent strain of SV. Infection of C6 cells with SVNI induced a selective translocation of PK...

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Bibliographic Details
Published in:The Journal of biological chemistry 2002-06, Vol.277 (26), p.23693-23701
Main Authors: Zrachia, Avi, Dobroslav, Melamed, Blass, Michal, Kazimirsky, Gila, Kronfeld, Ilana, Blumberg, Peter M, Kobiler, David, Lustig, Shlomo, Brodie, Chaya
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Biological Transport
Caspase 3
Caspases - metabolism
Chlorocebus aethiops
Enzyme Activation
Glioma - pathology
Glioma - virology
Isoenzymes - physiology
Phosphorylation
Protein Kinase C - physiology
Protein Kinase C-delta
Sindbis Virus - pathogenicity
Tyrosine - metabolism
Vero Cells
Virus Replication
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Summary:Sindbis virus (SV) is an alpha virus used as a model for studying the role of apoptosis in virus infection. In this study, we examined the role of protein kinase C (PKC) in the apoptosis induced by SVNI, a virulent strain of SV. Infection of C6 cells with SVNI induced a selective translocation of PKCdelta to the endoplasmic reticulum and its tyrosine phosphorylation. The specific PKCdelta inhibitor rottlerin and a PKCdelta kinase-dead mutant increased the apoptosis induced by SVNI. To examine the role of the tyrosine phosphorylation of PKCdelta in the apoptosis induced by SVNI we used a PKCdelta mutant in which five tyrosine residues were mutated to phenylalanine (PKCdelta5). PKCdelta5-overexpressing cells exhibited increased apoptosis in response to SVNI as compared with control cells and to cells overexpressing PKCdelta. SVNI also increased the cleavage of caspase 3 in cells overexpressing PKCdelta5 but did not induce cleavage of PKCdelta or PKCdelta5. Using single tyrosine mutants, we identified tyrosines 52, 64, and 155 as the phosphorylation sites associated with the apoptosis induced by SVNI. We conclude that PKCdelta exerts an inhibitory effect on the apoptosis induced by SV and that phosphorylation of PKCdelta on specific tyrosines is required for this function.
ISSN:0021-9258
DOI:10.1074/jbc.M111658200