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学科主题: 基础医学
题名:
Interaction between protein kinase C mu and the vanilloid receptor type 1
作者: Wang, Y1; Kedei, N1; Wang, M1; Wang, QJ1; Huppler, AR1; Toth, A1; Tran, R1; Blumberg, PM1
刊名: JOURNAL OF BIOLOGICAL CHEMISTRY
发表日期: 2004-12-17
DOI: 10.1074/jbc.M410331200
卷: 279, 期:51, 页:53674-53682
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology
研究领域[WOS]: Biochemistry & Molecular Biology
关键词[WOS]: ACTIVATION LOOP SER(744) ; DIRECT PHOSPHORYLATION ; D PKD ; EPSILON ; CELLS ; VR1 ; IDENTIFICATION ; EXPRESSION ; SUBSTRATE ; NEURONS
英文摘要:

The capsaicin receptor VR1 is a polymodal nociceptor activated by multiple stimuli. It has been reported that protein kinase C plays a role in the sensitization of VR1. Protein kinase D/PKCmu is a member of the protein kinase D serine/threonine kinase family that exhibits structural, enzymological, and regulatory features distinct from those of the PKCs, with which they are related. As part of our effort to optimize conditions for evaluating VR1 pharmacology, we found that treatment of Chinese hamster ovary (CHO) cells heterologously expressing rat VR1 (CHO/rVR1) with butyrate enhanced rVR1 expression and activity. The expression of PKCmu and PKCbeta1, but not of other PKC isoforms, was also enhanced by butyrate treatment, suggesting the possibility that these two isoforms might contribute to the enhanced activity of rVR1. In support of this hypothesis, we found the following. 1) Overexpression of PKCmu enhanced the response of rVR1 to capsaicin and low pH, and expression of a dominant negative variant of PKCmu reduced the response of rVR1. 2) Reduction of endogenous PKCmu using antisense oligonucleotides decreased the response of exogenous rVR1 expressed in CHO cells as well as of endogenous rVR1 in dorsal root ganglion neurons. 3) PKCmu localized to the plasma membrane when overexpressed in CHO/rVR1 cells. 4) PKCmu directly bound to rVR1 expressed in CHO cells as well as to endogenous rVR1 in dorsal root ganglia or to an N-terminal fragment of rVR1, indicating a direct interaction between PKCmu and rVR1. 5) PKCmu directly phosphorylated rVR1 or a longer N-terminal fragment ( amino acids 1-118) of rVR1 but not a shorter one (amino acids 1-99). 6) Mutation of S116A in rVR1 blocked both the phosphorylation of rVR1 by PKCmu and the enhancement by PKCmu of the rVR1 response to capsaicin. We conclude that PKCmu functions as a direct modulator of rVR1.

语种: 英语
WOS记录号: WOS:000225680600104
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51151
Appears in Collections:基础医学院_神经生物学系_期刊论文

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作者单位: 1.NCI, NIH, Bethesda, MD 20892 USA
2.Peking Univ, Dept Neurobiol, Neurosci Res Inst, Beijing 100083, Peoples R China

Recommended Citation:
Wang, Y,Kedei, N,Wang, M,et al. Interaction between protein kinase C mu and the vanilloid receptor type 1[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2004,279(51):53674-53682.
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