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The membrane organization of leukotriene synthesis

Mandal, Asim K ; Skoch, Jesse ; Bacskai, Brian J ; Hyman, Bradley T ; Christmas, Peter ; Miller, Douglas ; Yamin, Ting-Ting D ; Xu, Shihua ; Wisniewski, Douglas ; Evans, Jilly F ; Soberman, Roy J

Proceedings of the National Academy of Sciences of the United States of America, 27 April 2004, Vol.101(17), pp.6587-92 [Peer Reviewed Journal]

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  • Title:
    The membrane organization of leukotriene synthesis
  • Author: Mandal, Asim K ; Skoch, Jesse ; Bacskai, Brian J ; Hyman, Bradley T ; Christmas, Peter ; Miller, Douglas ; Yamin, Ting-Ting D ; Xu, Shihua ; Wisniewski, Douglas ; Evans, Jilly F ; Soberman, Roy J
  • Description: Cell signaling leading to the formation of leukotriene (LT)C(4) requires the localization of the four key biosynthetic enzymes on the outer nuclear membrane and endoplasmic reticulum. Whether any macromolecular organization of these proteins exists is unknown. By using fluorescence lifetime imaging microscopy and biochemical analysis, we demonstrate the presence of two distinct multimeric complexes that regulate the formation of LTs in RBL-2H3 cells. One complex consists of multimers of LTC(4) synthase and the 5-lipoxygenase activating protein (FLAP). The second complex consists of multimers of FLAP. Surprisingly, all LTC(4) synthase was found to be in association with FLAP. The results indicate that the formation of LTC(4) and LTB(4) may be determined by the compartmentalization of biosynthetic enzymes in discrete molecular complexes.
  • Is Part Of: Proceedings of the National Academy of Sciences of the United States of America, 27 April 2004, Vol.101(17), pp.6587-92
  • Identifier: ISSN: 0027-8424 ; PMID: 15084748 Version:1
  • Subjects: Leukotriene C4 -- Biosynthesis
  • Language: English

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