Hardy, Pierre-Olivier; Diallo, Tamsir O; Matte, Christine et Descoteaux, Albert 
ORCID: https://orcid.org/0000-0002-0633-5309
(2009).
Roles of phosphatidylinositol 3-kinase and p38 mitogen- activated protein kinase in the regulation of protein kinase C-alpha activation in interferon-gamma-stimulated macrophages
Immunology
, vol. 128
, nº Suppl 1.
e652-e660.
DOI: 10.1111/j.1365-2567.2009.03055.x.
Résumé
P>Members of the protein kinase C (PKC) family are activated by interferon-gamma (IFN-gamma) and modulate IFN-gamma- induced cellular responses by regulating the activity of transcription factors. We previously reported that PKC-alpha enhances the ability of IFN regulatory factor-1 to transactivate the class II transactivator (CIITA) promoter IV in IFN-gamma-stimulated macrophages. In addition, we showed that IFN-gamma induces the nuclear translocation of PKC-alpha but the mechanisms for this remain to be elucidated. In this study, we sought to identify signalling pathways involved in IFN-gamma-induced activation of PKC- alpha and to characterize their potential roles in modulating IFN-gamma-induced responses in macrophages. IFN- gamma-mediated nuclear translocation of PKC-alpha was a Janus activated kinase 2 (JAK2)-independent process, which required phosphatidylinositol 3-kinase (PI3K) and p38 mitogen-activated protein kinase (MAPK). However, PKC-alpha phosphorylation was independent of PI3K and p38 MAPK, indicating that IFN-gamma-induced phosphorylation and nuclear translocation of PKC-alpha are mediated by distinct mechanisms. In addition, inhibition of PI3K, but not of p38 MAPK, strongly impaired IFN-gamma-induced CIITA and MHC II gene expression. Finally, PKC-alpha associated with signal transducer and activator of transcription 1 (STAT1) and was required for the phosphorylation of STAT1 on serine 727 in IFN-gamma-stimulated macrophages. Taken together, our data indicate that PI3K and p38 MAPK modulate IFN-gamma- stimulated PKC-alpha nuclear translocation independently of JAK2 activity and that both PI3K and PKC-alpha are required for type IV CIITA and MHC II gene expression in IFN-gamma- stimulated macrophages.
| Type de document: | Article |
|---|---|
| Mots-clés libres: | - |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 30 juin 2024 21:10 |
| Dernière modification: | 30 juin 2024 21:10 |
| URI: | https://espace.inrs.ca/id/eprint/14744 |
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