PICK1, an anchoring protein that specifically targets protein kinase Cα to mitochondria selectively upon serum stimulation in NIH 3T3 cells

Wei Li Wang, Sheau Farn Yeh, Yuan I. Chang, Shun Fang Hsiao, Wei Nan Lian, Chi Hung Lin, Chi Ying F. Huang, Wey Jinq Lin*

*Corresponding author for this work

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

PICK1 binds to protein kinase Cα (PKCα) through the carboxylate-binding loop in its PDZ (PSD95/Disc-large/ZO-1) domain and the C terminus of PKCα. 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 PKCα to a particular intracellular compartment in addition to regulating PKC activity, we examine the localization of PICK1 and PKCα 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 PKCα 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 PKCα is concomitantly found in the condense perinuclear region. The C terminal-deleted PKCα fails to translocate and remains a diffuse cytoplasmic distribution, indicating that a direct interaction between PICK1 and PKCα is required for PKCα anchoring to mitochondria. 12-O-Tetradecanoylphorbol-13-acetate stimulation, in contrast, causes translocation of PKCα to the plasma membrane, whereas the majority of PICK1 remains in a cytoplasmic punctate pattern. Deletion at the C terminus of PKCα has no effect on 12-O-tetradecanoylphorbol-13-acetate-induced translocation. These findings indicate a previously unidentified role for PICK1 in anchoring PKCα to mitochondria in a ligand-specific manner.

Original languageEnglish
Pages (from-to)37705-37712
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number39
DOIs
StatePublished - 26 Sep 2003

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