Kabarowski J H, Zhu K, Le L Q, Witte O N, Xu Y
Department of Microbiology, Immunology, and Molecular Genetics, Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Science. 2001 Jul 27;293(5530):702-5. doi: 10.1126/science.1061781.
Although the biological actions of the cell membrane and serum lipid lysophosphatidylcholine (LPC) in atherosclerosis and systemic autoimmune disease are well recognized, LPC has not been linked to a specific cell-surface receptor. We show that LPC is a high-affinity ligand for G2A, a lymphocyte-expressed G protein-coupled receptor whose genetic ablation results in the development of autoimmunity. Activation of G2A by LPC increased intracellular calcium concentration, induced receptor internalization, activated ERK mitogen-activated protein kinase, and modified migratory responses of Jurkat T lymphocytes. This finding implicates a role for LPC-G2A interaction in the etiology of inflammatory autoimmune disease and atherosclerosis.
尽管细胞膜和血清脂质溶血磷脂酰胆碱（LPC）在动脉粥样硬化和全身性自身免疫性疾病中的生物学作用已得到充分认识，但LPC尚未与特定的细胞表面受体相关联。我们发现，LPC是G2A的高亲和力配体，G2A是一种淋巴细胞表达的G蛋白偶联受体，其基因缺失会导致自身免疫的发展。LPC对G2A的激活增加了细胞内钙浓度，诱导了受体内化，激活了ERK丝裂原活化蛋白激酶，并改变了Jurkat T淋巴细胞的迁移反应。这一发现表明LPC-G2A相互作用在炎症性自身免疫疾病和动脉粥样硬化的病因学中起作用。
