期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 280, 期 6, 页码 4415-4421出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M408246200
关键词
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Lysophosphatidic acid (LPA) is an abundant cellular lipid with a myriad of biological effects. It plays an important role in both inter- and intracellular signaling. Activation of the LPA(1-3) G-protein-coupled receptors explains many of the extracellular effects of LPA, including cell growth, differentiation, survival, and motility. However, LPA also acts intracellularly, activating the nuclear hormone receptor peroxisome proliferator-activated receptor-gamma that regulates gene transcription. This study shows that the novel subfamily of mechano-gated K-2p channels comprising TREK-1, TREK-2, and TRAAK is strongly activated by intracellular LPA. The LPA-activated 2P domain K+ channels are intracellular ligandgated K+ channels such as the Ca2+ - or the ATP-sensitive K+ channels. LPA reversibly converts these mechano-gated, pH- and voltage-sensitive channels into leak conductances. Gating conversion of the 2P domain K+ channels by intracellular LPA represents a novel form of ion channel regulation. Thus, the TREK and TRAAK channels should be included in the LPA-associated physiological and disease states.
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