Activation of protein kinase Cδ by IFN-γ

Dilip K. Deb, Antonella Sassano, Fatima Lekmine, Beata Majchrzak, Amit Verma, Suman Kambhampati, Shahab Uddin, Arshad Rahman, Eleanor N. Fish, Leonidas C. Platanias

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106 Scopus citations

Abstract

Engagement of the type II IFN (IFN-γ) receptor results in activation of the Janus kinase-Stat pathway and induction of gene transcription via IFN-γ-activated site (GAS) elements in the promoters of IFN-γ-inducible genes. An important event in IFN-γ-dependent gene transcription is phosphorylation of Stat1 on Ser727, 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-γ signaling. Our data demonstrate that PKCδ is rapidly phosphorylated during engagement of the type II IFNR and its kinase domain is induced. Subsequently, the activated PKCδ associates with a member of the Stat family of proteins, Stat1, which acts as a substrate for its kinase activity and undergoes phosphorylation on Ser727. Inhibition of PKCδ activity diminishes phosphorylation of Stat1 on Ser727 and IFN-γ-dependent transcriptional regulation via IFN-γ-activated site elements, without affecting the phosphorylation of the protein on Tyr701. Thus, PKCδ is activated during engagement of the IFN-γ receptor and plays an important role in IFN-γ signaling by mediating serine phosphorylation of Stat1 and facilitating transcription of IFN-γ-stimulated genes.

Original languageEnglish (US)
Pages (from-to)267-273
Number of pages7
JournalJournal of Immunology
Volume171
Issue number1
StatePublished - Jul 1 2003
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Deb, D. K., Sassano, A., Lekmine, F., Majchrzak, B., Verma, A., Kambhampati, S., Uddin, S., Rahman, A., Fish, E. N., & Platanias, L. C. (2003). Activation of protein kinase Cδ by IFN-γ. Journal of Immunology, 171(1), 267-273.