Activation of protein kinase C delta by IFN-gamma.

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.
Mesh Terms:
Acetophenones, Benzopyrans, Carbazoles, DNA-Binding Proteins, Enzyme Activation, Enzyme Inhibitors, Humans, Imidazoles, Indoles, Interferon-gamma, Isoenzymes, Mesylates, Phosphatidylinositol 3-Kinases, Phosphorylation, Phosphoserine, Protein Kinase C, Protein Kinase C-delta, Pyridines, Pyrroles, Receptors, Interferon, STAT1 Transcription Factor, Signal Transduction, Trans-Activators, Tumor Cells, Cultured
J. Immunol.
Date: Jul. 01, 2003
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