Activation of protein kinase Cδ by IFN-γ

被引:107
作者
Deb, DK
Sassano, A
Lekmine, F
Majchrzak, B
Verma, A
Kambhampati, S
Uddin, S
Rahman, A
Fish, EN
Platanias, LC
机构
[1] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Sch Med, Chicago, IL 60611 USA
[2] Northwestern Univ, Div Hematol Oncol, Sch Med, Chicago, IL 60611 USA
[3] Lakeside Vet Adm Med Ctr, Chicago, IL 60611 USA
[4] Univ Illinois, Hematol Oncol Sect, Chicago, IL 60607 USA
[5] Univ Illinois, Dept Pharmacol, Chicago, IL 60607 USA
[6] Univ Hlth Network, Toronto Gen Res Inst, Div Cell & Mol Biol, Toronto, ON, Canada
[7] Univ Toronto, Dept Immunol, Toronto, ON, Canada
关键词
D O I
10.4049/jimmunol.171.1.267
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Engagement of the type 11 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 11 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, PKCS 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 WN-gamma-stimulated genes.
引用
收藏
页码:267 / 273
页数:7
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