PICK1 binds to protein kinase C␣ (PKC␣) through the carboxylate-binding loop in its PDZ (PSD95/Disc-large/ ZO-1) domain and the C terminus of PKC␣. 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 PKC␣ to a particular intracellular compartment in addition to regulating PKC activity, we examine the localization of PICK1 and PKC␣ 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 carboxylatebinding loop do not have an effect, suggesting that PICK1 can bind PKC␣ 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 PKC␣ is concomitantly found in the condense perinuclear region. The C terminal-deleted PKC␣ fails to translocate and remains a diffuse cytoplasmic distribution, indicating that a direct interaction between PICK1 and PKC␣ is required for PKC␣ anchoring to mitochondria. 12-O-Tetradecanoylphorbol-13-acetate stimulation, in contrast, causes translocation of PKC␣ to the plasma membrane, whereas the majority of PICK1 remains in a cytoplasmic punctate pattern. Deletion at the C terminus of PKC␣ has no effect on 12-O-tetradecanoylphorbol-13-acetate-induced translocation. These findings indicate a previously unidentified role for PICK1 in anchoring PKC␣ to mitochondria in a ligandspecific manner.
[structure: see text]. Two novel triterpene dilactones, kadsuphilactones A (1) and B (2), were isolated from the Taiwanese medicinal plant Kadsura philippinensis. The structures of 1 and 2 were elucidated on the basis of extensive spectroscopic methods, including two-dimensional NMR techniques, and confirmed by X-ray crystallographic analysis. Kadsuphilactone B (2) exhibited in vitro anti-HBV activity with IC(50) values of 6 microg/mL by HBsAg enzyme immunoassay.
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