期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 105, 期 51, 页码 20434-20439出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0808211106
关键词
inflammation; multiprotein complex; 5-lipoxygenase; 5-lipoxygenase-activating protein
资金
- National Institutes of Health [R56 AI068771, R01 AI068771, 5R01 GM61823, 5P50 NS010828, 5R01 AG08487, 5R01 EB000768, R01 AI 059746, P01 AI065858, T32 DK001540]
- Merck Research Labs, Rahway NJ
- Merck and Merck Frosst
- Fidelity Foundation
- Arthritis Foundation Fellowship
Leukotrienes (LTs) are signaling molecules derived from arachidonic acid that initiate and amplify innate and adaptive immunity. In turn, how their synthesis is organized on the nuclear envelope of myeloid cells in response to extracellular signals is not understood. We define the supramolecular architecture of LT synthesis by identifying the activation-dependent assembly of novel multiprotein complexes on the outer and inner nuclear membranes of mast cells. These complexes are centered on the integral membrane protein 5-Lipoxygenase-Activating Protein, which we identify as a scaffold protein for 5-Lipoxygenase, the initial enzyme of LT synthesis. We also identify these complexes in mouse neutrophils isolated from inflamed joints. Our studies reveal the macromolecular organization of LT synthesis.
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