國家衛生研究院 NHRI:Item 3990099045/2268
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    題名: PICK1, an anchoring protein that specifically targets protein kinase C alpha to mitochondria selectively upon serum stimulation in NIH 3T3 cells
    作者: Wang, WL;Yeh, SF;Chang, YI;Hsiao, SF;Lian, WN;Lin, CH;Huang, CYF;Lin, WJ
    貢獻者: Division of Molecular and Genomic Medicine
    摘要: PICK1 binds to protein kinase Calpha (PKCalpha) through the carboxylate-binding loop in its PDZ (PSD95/Disc-large/ZO-1) domain and the C terminus of PKCalpha. We have previously shown that PICK1 modulates the catalytic activity of PKC selectively toward the antiproliferative gene TIS21. To investigate whether PICK1 plays a role in targeting activated PKCalpha to a particular intracellular compartment in addition to regulating PKC activity, we examine the localization of PICK1 and PKCalpha in response to various stimuli. Double staining with organelle markers and anti-rPICK1 antibodies reveals that PICK1 is associated with mitochondria but not with endoplasmic reticulum or Golgi in NIH 3T3 cells. Deletion of the PDZ domain impairs the mitochondria localization of PICK1, whereas mutations in the carboxylate-binding loop do not have an effect, suggesting that PICK1 can bind PKCalpha and mitochondria simultaneously. Upon serum stimulation, PICK1 translocates and displays a dense ring-like structure around the nucleus, where it still associates with mitochondria. A substantial portion of PKCalpha is concomitantly found in the condense perinuclear region. The C terminal-deleted PKCalpha fails to translocate and remains a diffuse cytoplasmic distribution, indicating that a direct interaction between PICK1 and PKCalpha is required for PKCalpha anchoring to mitochondria. 12-O-Tetradecanoylphorbol-13-acetate stimulation, in contrast, causes translocation of PKCalpha to the plasma membrane, whereas the majority of PICK1 remains in a cytoplasmic punctate pattern. Deletion at the C terminus of PKCalpha has no effect on 12-O-tetradecanoylphorbol-13-acetate-induced translocation. These findings indicate a previously unidentified role for PICK1 in anchoring PKCalpha to mitochondria in a ligand-specific manner.
    關鍵詞: Biochemistry & Molecular Biology
    日期: 2003-09-26
    關聯: Journal of Biological Chemistry. 2003 Sep;278(39):37705-37712.
    Link to: http://dx.doi.org/10.1074/jbc.M304619200
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1083-351X&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000185437200087
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0141844501
    顯示於類別:[黃奇英(1998-2005)] 期刊論文

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