RRC ID 12734
著者 Irie A, Harada K, Tsukamoto H, Kim JR, Araki N, Nishimura Y.
タイトル Protein kinase D2 contributes to either IL-2 promoter regulation or induction of cell death upon TCR stimulation depending on its activity in Jurkat cells.
ジャーナル Int Immunol
Abstract Members of protein kinase D (PKD) family serine/threonine kinases (PKD1, PKD2 and PKD3) are expressed in wide range of cells and regulate various cellular responses including immune responses. We have previously shown that PKD is involved in the signaling pathways of a human CD4(+) T cell clone stimulated with its cognate antigen. Contrary to foregoing publications, PKD1 mRNA was not detected in human T cells, Jurkat cells and mouse thymocytes and splenocytes. Instead, mass-spectrometric and reverse transcription-PCR analyses revealed that PKD2 was predominant in T cells. To investigate the roles of PKD2, wild-type (WT) and constitutively active (CA) PKD2 were expressed in Jurkat cells together with IL-2 promoter-driven reporter gene. Expression of WT-PKD2 enhanced IL-2 promoter activity upon stimulation with anti-CD3 mAb, while expression of CA-PKD2 inhibited IL-2 promoter activity and induced cell death. Although the cell death was suppressed by the treatment with caspase inhibitor, the IL-2 promoter activity was rarely recovered in CA-PKD2-expressing cells upon TCR stimulation. WT-PKD2 localized mainly in the cytoplasm translocated into the nucleus after TCR stimulation, while CA-PKD2 was present in both the cytoplasm and the nuclei before and after stimulation. Proteomic analyses revealed that CA-PKD2 enhanced the amount of phosphorylated SET protein, a histone chaperon that regulates histone acetylation, in Jurkat cells and the recombinant SET protein was phosphorylated by CA-PKD2 in vitro. The data provide a renewing insight into the subset of PKD family kinases expressed in T cells and suggest that PKD2 is involved in IL-2 promoter regulation and cell death depending on its activity upon TCR stimulation.
巻・号 18(12)
ページ 1737-47
公開日 2006-12-1
DOI 10.1093/intimm/dxl108
PII dxl108
PMID 17077180
MeSH Animals Cell Death Cell Line Gene Expression Regulation* HeLa Cells Humans Interleukin-2 / genetics Interleukin-2 / metabolism* Jurkat Cells Mice Mice, Inbred C57BL Promoter Regions, Genetic* Protein Kinase D2 Protein Kinases / genetics Protein Kinases / metabolism* Receptors, Antigen, T-Cell / immunology* T-Lymphocytes / immunology T-Lymphocytes / physiology
IF 3.519
引用数 17
WOS 分野 IMMUNOLOGY
リソース情報
遺伝子材料 CSII-CMV-RfA (RDB04386) CSII-EF-RfA (RDB04387) pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394)