Saba J D, Nara F, Bielawska A, Garrett S, Hannun Y A
Duke University Medical Center, Durham, North Carolina 27710, USA.
J Biol Chem. 1997 Oct 17;272(42):26087-90. doi: 10.1074/jbc.272.42.26087.
Sphingolipids elicit a wide variety of eukaryotic cellular responses, most involving regulation of cell growth, differentiation, and apoptosis. Sphingosine 1-phosphate, a sphingolipid catabolite, is mitogenic in fibroblasts and inhibits the chemotactic mobility and invasiveness of human tumor cells. Sphingosine 1-phosphate degradation requires cleavage at the C2-3 carbon bond by sphingosine phosphate lyase. A yeast genetic approach was used to clone the first sphingosine phosphate lyase gene, BST1. BST1 overexpression conferred resistance to sphingosine in yeast. BST1 deletion produced sensitivity to exogenous D-erythro-sphingosine and phytosphingosine and intracellular accumulation of sphingosine 1-phosphate upon exposure to exogenous sphingosine. This study confirms that sphingoid base metabolism is similar in all eukaryotes and suggests that yeast genetics may be useful in the isolation and identification of other genes involved in sphingolipid signaling and metabolism.
鞘脂引发多种真核细胞反应,其中大多数涉及细胞生长、分化和凋亡的调控。鞘氨醇1 - 磷酸,一种鞘脂分解代谢产物,对成纤维细胞有促有丝分裂作用,并抑制人类肿瘤细胞的趋化移动性和侵袭性。鞘氨醇1 - 磷酸的降解需要鞘氨醇磷酸裂解酶在C2 - 3碳键处进行切割。采用酵母遗传学方法克隆了首个鞘氨醇磷酸裂解酶基因BST1。BST1的过表达赋予酵母对鞘氨醇的抗性。BST1基因缺失导致酵母对外源D - 赤藓糖鞘氨醇和植物鞘氨醇敏感,且在暴露于外源鞘氨醇时细胞内鞘氨醇1 - 磷酸积累。这项研究证实所有真核生物中鞘脂碱基代谢相似,并表明酵母遗传学可能有助于分离和鉴定参与鞘脂信号传导和代谢的其他基因。