Photolysis of intracellular caged sphingosine-1-phosphate causes Ca2+ mobilization independently of G-protein-coupled receptors
Photolysis of intracellular caged sphingosine-1-phosphate causes Ca2+ mobilization independently of G-protein-coupled receptors
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DOI：
10.1016/s0014-5793(03)01219-5
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发表时间：
2003-11-20
期刊：
影响因子：
3.5
通讯作者：
Jakobs, KH
中科院分区：
文献类型：
--
作者：
Heringdorf, DMZ;Liliom, K;Jakobs, KH
鞘氨醇-1-磷酸(SIP)是鞘氨醇激酶的产物，可激活多种广泛表达的G蛋白偶联受体(GPCRs)。Sip也可能扮演第二信使的角色，但最近的发现挑战了这一假说。在这里，我们证明了细胞内的SIP可以独立于S1P-GPCR而动员完整细胞中的钙离子。在几秒钟内，笼状SIP光解产生的SIP使HEK-293、SKNMC和HepG2细胞内游离钙离子浓度升高，对细胞外作用的SIP的反应被阻断或消失。笼状SIP的光解诱导的钙瞬变是由thapsigargin敏感库中的钙动员引起的。这些结果为SIP真正的细胞内作用提供了直接证据。(C)2003年欧洲生化学会联合会。爱思唯尔出版，版权所有。
Sphingosine-1-phosphate (SIP), the product of sphingosine kinase, activates several widely expressed G-protein-coupled receptors (GPCR). SIP might also play a role as second messenger, but this hypothesis has been challenged by recent findings. Here we demonstrate that intracellular SIP can mobilize Ca2+ in intact cells independently of S1P-GPCR. Within seconds, SIP generated by the photolysis of caged SIP raised the intracellular free Ca2+ concentration in HEK-293, SKNMC and HepG2 cells, in which the response to extracellularly applied SIP was either blocked or absent. Ca2+ transients induced by photolysis of caged SIP were caused by Ca2+ mobilization from thapsigargin-sensitive stores. These results provide direct evidence for a true intracellular action of SIP. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.