Sphingosine kinase 1 localized to the plasma membrane lipid raft microdomain overcomes serum deprivation induced growth inhibition.
Sphingosine kinase 1 localized to the plasma membrane lipid raft microdomain overcomes serum deprivation induced growth inhibition.
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DOI：
10.1016/j.abb.2009.09.013
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发表时间：
2009-12
影响因子：
3.9
通讯作者：
Yun JK
中科院分区：
文献类型：
--
作者：
Hengst JA;Guilford JM;Fox TE;Wang X;Conroy EJ;Yun JK
一些研究表明，鞘氨醇激酶1（SphK 1）易位到质膜（PM）激活后，并进一步建议质膜脂筏微区（PMLRM）作为SphK 1重新定位的目标。然而，迄今为止，SphK 1本地化的PMLRM的直接证据一直缺乏。在这份报告中，使用多种生物化学和亚细胞分级分离技术，我们证明，内源性SphK 1蛋白及其底物，D-β-鞘氨醇，存在于PMLRM内。此外，我们表明，PMA刺激SphK 1定位于PMLRM的结果在生产鞘氨醇-1-磷酸以及诱导血清剥夺条件下的细胞生长。我们进一步报道，Ser 225 Ala和Thr 54 Cys突变，据报道废除磷脂酰丝氨酸结合，阻止SphK 1靶向PMLRM和SphK 1诱导的细胞生长。总之，这些发现提供了直接的证据，PMLRM是SphK 1克服血清剥夺细胞生长抑制的主要作用位点。
Several studies have demonstrated that sphingosine kinase 1 (SphK1) translocates to the plasma membrane (PM) upon its activation and further suggested the plasma membrane lipid raft microdomain (PMLRM) as a target for SphK1 relocalization. To date, however, direct evidence of SphK1 localization to the PMLRM has been lacking. In this report, using multiple biochemical and subcellular fractionation techniques we demonstrate that endogenous SphK1 protein and its substrate, D-erythro sphingosine, are present within the PMLRM. Additionally, we demonstrate that the PMA stimulation of SphK1 localized to the PMLRM results in production of sphingosine-1-phosphate as well as induction of cell growth under serum-deprivation conditions. We further report that Ser225Ala and Thr54Cys mutations, reported to abrogate phosphatidylserine binding, block SphK1 targeting to the PMLRM and SphK1 induced cell growth. Together these findings provide direct evidence that the PMLRM is the major site-of-action for SphK1 to overcome serum-deprived cell growth inhibition.
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DOI：
10.1083/jcb.93.1.97
发表时间：
1982-04
期刊：
The Journal of cell biology
影响因子：
--
作者：
Fujiki Y;Hubbard AL;Fowler S;Lazarow PB
通讯作者：
Lazarow PB
影响因子：
64.8
作者：
OLIVERA, A;SPIEGEL, S
通讯作者：
SPIEGEL, S
影响因子：
10.8
作者：
Jin, Zhu-Qiu;Karliner, Joel S.
通讯作者：
Karliner, Joel S.
影响因子：
4.1
作者：
Banno, Y;Kato, M;Nozawa, Y
通讯作者：
Nozawa, Y
DOI：
10.1016/j.bbrc.2003.09.194
发表时间：
2003-11-07
影响因子：
3.1
作者：
Inagaki, Y;Li, PY;Igarashi, Y
通讯作者：
Igarashi, Y