Title: High affinity receptor for IgE stimulation activates protein kinase D augmenting activator protein-1 activity for cytokine producing in mast cells
Authors: Yamashita, Kyoko
Gon, Yasuhiro
Shimokawa, Toshibumi
Nunomura, Satoshi
Endo, Daisuke
Miyata, Naoko
Hashimoto, Shu
Van Lint, Johan
Ra, Chisei # ×
Issue Date: Mar-2010
Publisher: Elsevier Science
Series Title: International Immunopharmacology vol:10 issue:3 pages:277-283
Abstract: Protein kinase D (PKD) is a serine-threonine kinase involved in the activation of a variety of cells. In mast cells, activation of PKD by cross-linking of high affinity receptor for IgE (FcepsilonRI) has been reported, but little is known for its effects on cytokine production. We investigated the roles of PKD on FcepsilonRI-induced activator protein-1 (AP-1) activation and proinflammatory cytokine productions in mast cells. Pharmacological inhibition of PKD strongly inhibited production of interleukin (IL)-13 and tumor necrosis factor (TNF)-alpha induced by FcepsilonRI stimulation, and the overexpression of PKD significantly increased the IL-13 and TNF-alpha production. Reporter assay revealed that the overexpression of PKD enhanced FcepsilonRI-induced IL-13 promoter activation, and that the 5'-flanking region of IL-13 gene from positions -110 to -52 was under the regulation of PKD. The overexpression of PKD enhanced the induction of AP-1 luciferase activity by FcepsilonRI stimulation, while it had no effect on luciferase activities dependent upon NF-kappaB and NF-AT activated by FcepsilonRI stimulation. In EMSA, c-Jun and c-Fos appear to be the major components of AP-1 complexes activated by FcepsilonRI stimulation. Moreover the overexpression of PKD strongly enhanced the phosphorylation of both c-Jun and c-Fos following FcepsilonRI stimulation. Although stress-activated protein kinase/c-Jun N-terminal kinase (JNK) is known to be an important regulator for c-Jun phosphorylation and AP-1 activation, overexpression and inhibition of PKD had no effects on JNK phosphorylation. These results suggest that PKD may play a pivotal role in FcepsilonRI-induced cytokine production in mast cells through the activation of c-Jun, c-Fos, and AP-1.
ISSN: 1567-5769
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Protein Phosphorylation and Proteomics
× corresponding author
# (joint) last author

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