Sphingolipid receptor signaling and function in human bladder carcinoma cells: inhibition of LPA- but enhancement of thrombin-stimulated cell motility
Sphingolipid receptor signaling and function in human bladder carcinoma cells: inhibition of LPA- but enhancement of thrombin-stimulated cell motility
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人膀胱癌细胞中的鞘脂受体信号传导和功能：抑制 LPA，但增强凝血酶刺激的细胞运动
DOI：
10.1007/s002109900159
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
K. Jakobs
中科院分区：
文献类型：
--
作者：
U. Rümenapp;G. Lümmen;S. Virchow;Jan Hanske;D. M. Heringdorf;K. Jakobs
摘要。sphingosin -1-磷酸（SPP）诱导多种细胞反应，包括Ca2+信号，增殖和运动抑制，显然是通过作用于特定的G蛋白偶联受体。在这里，研究人员检测了人膀胱癌（J82）细胞中鞘脂受体的表达、信号传导和运动反应，其中溶血磷脂酸（LPA）和凝血酶是有效的激动剂。SPP能快速动员Ca2+，刺激磷脂酶C和D，抑制cAMP的积累，而不影响J82细胞的生长，这些细胞表达最近发现的SPP受体Edg-1和Edg-3。百日咳毒素（PTX）对SPP的作用有强减毒作用，而脊髓鞘甲磷胆碱（SPPC）可模拟SPP的作用。SPP和SPPC本身诱导了小的、ptx敏感的运动反应。然而，LPA对细胞运动的刺激被SPP和SPPC阻断，而LPA本身也对ptx敏感。相比之下，凝血酶本身对ptx不敏感，但它的运动刺激被鞘脂以ptx敏感的方式强烈增强。LPA-和凝血酶刺激的运动的双向调节不是由于控制细胞运动的Rho gtpase激活的选择性改变。事实上，LPA和凝血酶诱导的RhoA活化和rho依赖性肌动蛋白应激纤维的形成是模拟的，但SPP和SPPC没有改变。我们得出结论，J82细胞表达鞘脂受体，通过G蛋白偶联到几种信号通路。最重要的是，这些鞘脂受体有效地调节凝血酶和lpa刺激的运动，但方向相反，这表明这些人类膀胱癌细胞的迁移是由相互作用的细胞外配体的复杂网络控制的。
Abstract. Sphingosine-1-phosphate (SPP) induces a variety of cellular responses, including Ca2+ signaling, proliferation, and inhibition of motility, apparently by acting at specific G protein coupled receptors. Here, the expression, signaling, and motile responses of sphingolipid receptors were examined in human bladder carcinoma (J82) cells, for which lysophosphatidic acid (LPA) and thrombin act as potent agonists. SPP potently and rapidly mobilized Ca2+, stimulated phospholipases C and D, and inhibited cAMP accumulation, without affecting growth of J82 cells, which express the recently identified SPP receptors, Edg-1 and Edg-3. The effects of SPP were mimicked by sphingosylphosphorylcholine (SPPC) and strongly attenuated by pertussis toxin (PTX). SPP and SPPC by themselves induced a small, PTX-sensitive motile response. However, stimulation of cell motility by LPA, which by itself was also PTX-sensitive, was blocked by SPP and SPPC. In contrast, motility stimulation by thrombin, which by itself was PTX-insensitive, was strongly augmented by the sphingolipids in a PTX-sensitive manner. The bidirectional regulation of LPA- and thrombin-stimulated motility was not due to selective alterations in the activation of Rho GTPases which control cell motility. In fact, RhoA activation and Rho-dependent actin stress fiber formation induced by LPA and thrombin were mimicked, but not altered by SPP and SPPC. We conclude that J82 cells express sphingolipid receptors, coupled via G proteins to several signaling pathways. Most importantly, these sphingolipid receptors potently regulate thrombin- and LPA-stimulated motility, but in opposite directions, suggesting that migration of these human bladder carcinoma cells is controlled by a complex network of interacting extracellular ligands.
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影响因子：
56.9
作者：
Lee, MJ;Van Brocklyn, JR;Hla, T
通讯作者：
Hla, T
DOI：
10.1073/pnas.89.20.9686
发表时间：
1992-10-15
影响因子：
11.1
作者：
SADAHIRA, Y;RUAN, FQ;IGARASHI, Y
通讯作者：
IGARASHI, Y
影响因子：
20.3
作者：
Yutaka Yatomi;Fuqiang Ruan;S. Hakomori;Yasuyuki Igarashi
通讯作者：
Yutaka Yatomi;Fuqiang Ruan;S. Hakomori;Yasuyuki Igarashi
1-磷酸鞘氨醇通过受体偶联的细胞外作用并以百日咳毒素不敏感的方式调节黑色素瘤细胞的运动。
DOI：
10.1021/bi970926s
发表时间：
1997
期刊：
Biochemistry.
影响因子：
--
作者：
Yamamura,S;Yatomi,Y;Ruan,F;Sweeney,EA;Hakomori,S;Igarashi,Y
通讯作者：
Igarashi,Y
1-磷酸鞘氨醇是一种假定的第二信使，通过不依赖肌醇三磷酸的途径从内部储存中调动钙。
DOI：
--
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Mattie,M;Brooker,G;Spiegel,S
通讯作者：
Spiegel,S