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Updated: Aug 9, 2026

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
Published on: January 24, 2016
Activation of protein kinase C delta by IFN-gamma
Dilip K Deb1, Antonella Sassano, Fatima Lekmine
1Robert H. Lurie Comprehensive Cancer Center and Division of Hematology-Oncology, Northwestern University Medical School, Chicago, IL 60611, USA.
Abstract:
Engagement of the type II IFN (IFN-gamma) receptor results in activation of the Janus kinase-Stat pathway and induction of gene transcription via IFN-gamma-activated site (GAS) elements in the promoters of IFN-gamma-inducible genes. An important event in IFN-gamma-dependent gene transcription is phosphorylation of Stat1 on Ser(727), which is regulated by a kinase activated downstream of the phosphatidylinositol 3'-kinase. Here we provide evidence that a member of the protein kinase C (PKC) family of proteins is activated downstream of the phosphatidylinositol 3'-kinase and is engaged in IFN-gamma signaling. Our data demonstrate that PKCdelta is rapidly phosphorylated during engagement of the type II IFNR and its kinase domain is induced. Subsequently, the activated PKCdelta associates with a member of the Stat family of proteins, Stat1, which acts as a substrate for its kinase activity and undergoes phosphorylation on Ser(727). Inhibition of PKCdelta activity diminishes phosphorylation of Stat1 on Ser(727) and IFN-gamma-dependent transcriptional regulation via IFN-gamma-activated site elements, without affecting the phosphorylation of the protein on Tyr(701). Thus, PKCdelta is activated during engagement of the IFN-gamma receptor and plays an important role in IFN-gamma signaling by mediating serine phosphorylation of Stat1 and facilitating transcription of IFN-gamma-stimulated genes.
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