Meyer Zu Heringdorf Dagmar
Institut für Pharmakologie, Universitätsklinikum Essen, 45122 Essen, Germany.
J Cell Biochem. 2004 Aug 1;92(5):937-48. doi: 10.1002/jcb.20107.
Changes in cellular Ca(2+) concentrations form a ubiquitous signal regulating numerous processes such as fertilization, differentiation, proliferation, contraction, and secretion. The Ca(2+) signal, highly organized in space and time, is generated by the cellular Ca(2+) signaling toolkit. Lysophospholipids, such as sphingosine-1-phosphate (S1P), sphingosylphosphorylcholine (SPC), or lysophosphatidic acid (LPA) use this toolkit in a specific manner to initiate their cellular responses. Acting as agonists at G protein-coupled receptors, S1P, SPC, and LPA increase the intracellular free Ca(2+) concentration (Ca(2+)) by using the classical, phospholipase C (PLC)-dependent pathway as well as PLC-independent pathways such as sphingosine kinase (SphK)/S1P. The S1P(1) receptor, via protein kinase C, inhibits the Ca(2+) transients caused by other receptors. Both S1P and SPC also act intracellularly to regulate Ca(2+). Intracellular S1P mobilizes Ca(2+) in intact cells independently of G protein-coupled S1P receptors, and Ca(2+) signaling by many agonists requires SphK-mediated S1P production. As shown for the FcepsilonRI receptor, PLC and SphK may contribute specific components to the overall Ca(2+) transient. Of the many open questions, identification of the intracellular S1P target site(s) appears to be of particular importance.
细胞内钙离子浓度的变化形成了一种普遍存在的信号，可调节众多过程，如受精、分化、增殖、收缩和分泌。高度在空间和时间上组织化的钙离子信号是由细胞钙离子信号传导工具包产生的。溶血磷脂，如1-磷酸鞘氨醇（S1P）、鞘氨醇磷酸胆碱（SPC）或溶血磷脂酸（LPA），以特定方式利用该工具包来启动其细胞反应。作为G蛋白偶联受体的激动剂，S1P、SPC和LPA通过使用经典的、磷脂酶C（PLC）依赖性途径以及PLC非依赖性途径（如鞘氨醇激酶（SphK）/S1P）来增加细胞内游离钙离子浓度（[Ca²⁺]i）。S1P₁受体通过蛋白激酶C抑制由其他受体引起的[Ca²⁺]i瞬变。S1P和SPC也在细胞内起作用以调节[Ca²⁺]i。细胞内的S1P在完整细胞中独立于G蛋白偶联的S1P受体动员钙离子，并且许多激动剂的钙离子信号传导需要SphK介导的S1P产生。如在FcepsilonRI受体中所示，PLC和SphK可能对整体[Ca²⁺]i瞬变有特定贡献。在众多未解决的问题中，确定细胞内S1P靶位点似乎尤为重要。
