Blaukat A, Dikic I
Pharmakologisches Institut, Ruprecht-Karls-Universität Heidelberg, Germany.
Biol Chem. 2001 Jan;382(1):135-9. doi: 10.1515/BC.2001.020.
Sphingosine kinase phosphorylates sphingosine to generate sphingosine 1-phosphate, a phospholipid that has been implicated in signaling by a number of transmembrane receptors and was recently shown to act as a ligand for a specific class of G protein-coupled receptors. Here we show that the G protein-coupled bradykinin B2 receptor activates sphingosine kinase leading to a time- and dose-dependent elevation of cellular sphingosine 1-phosphate levels that was blocked by the sphingosine kinase inhibitor dihydrosphingosine. Furthermore, increasing doses of this inhibitor partially affected the bradykinin-mediated ERK/MAP kinase activation and fully blocked the protein kinase C-independent component of the signaling pathway from the B2 receptor to the ERK/MAP kinase cascade. Overexpression of sphingosine kinase did not additionally increase the bradykinin-induced ERK/MAP kinase activity, indicating a permissive rather than activating role of sphingosine 1-phosphate in B2 receptor-mediated mitogenic signaling.
鞘氨醇激酶将鞘氨醇磷酸化生成1-磷酸鞘氨醇，这是一种磷脂，与多种跨膜受体的信号传导有关，最近还被证明可作为一类特定G蛋白偶联受体的配体。我们在此表明，G蛋白偶联的缓激肽B2受体激活鞘氨醇激酶，导致细胞内1-磷酸鞘氨醇水平呈时间和剂量依赖性升高，而鞘氨醇激酶抑制剂二氢鞘氨醇可阻断这一升高。此外，该抑制剂剂量增加会部分影响缓激肽介导的ERK/MAP激酶激活，并完全阻断从B2受体到ERK/MAP激酶级联反应的信号通路中不依赖蛋白激酶C的成分。鞘氨醇激酶的过表达并未额外增加缓激肽诱导的ERK/MAP激酶活性，表明1-磷酸鞘氨醇在B2受体介导的促有丝分裂信号传导中起允许作用而非激活作用。
