Sahu Santosh Kumar, Gummadi Sathyanarayana N, Manoj N, Aradhyam Gopala Krishna
Department of Biotechnology, Indian Institute of Technology Madras, Chennai, India.
Arch Biochem Biophys. 2007 Jun 1;462(1):103-14. doi: 10.1016/j.abb.2007.04.002. Epub 2007 Apr 17.
Phospholipid scramblases are a group of homologous proteins that are conserved in all eukaryotic organisms. They are believed to be involved in destroying plasma membrane phospholipid asymmetry at critical cellular events like cell activation, injury and apoptosis. However, a detailed mechanism of phospholipid scrambling still awaits a proper understanding. The most studied member of this family, phospholipid scramblase 1 (PLSCR1) (a 37kDa protein), is involved in rapid Ca2+ dependent transbilayer redistribution of plasma membrane phospholipids. Recently the function of PLSCR1 as a phospholipids translocator has been challenged and evidences suggest that PLSCR1 acts as signaling molecule. It has been shown to be involved in protein phosphorylation and as a potential activator of genes in response to interferon and other cytokines. Interferon induced rapid biosynthesis of PLSCR1 targets some of the protein into the nucleus, where it binds to the promoter region of inositol 1,4,5-triphosphate (IP3) receptor type 1 (IP3R1) gene and induces its expression. Palmitoylation of PLSCR1 acts as a switch, controlling its localization either to the PM or inside the nucleus. In the present review, we discuss the current understanding of PLSCR1 in relation to its trafficking, localization and signaling functions.
磷脂翻转酶是一类在所有真核生物中都保守的同源蛋白。它们被认为在诸如细胞激活、损伤和凋亡等关键细胞事件中参与破坏质膜磷脂不对称性。然而，磷脂翻转的详细机制仍有待深入了解。该家族中研究最多的成员磷脂翻转酶1（PLSCR1）（一种37kDa的蛋白质），参与质膜磷脂快速的Ca2+依赖性跨膜重分布。最近，PLSCR1作为磷脂转运体的功能受到了挑战，有证据表明PLSCR1作为信号分子发挥作用。已表明它参与蛋白质磷酸化，并作为响应干扰素和其他细胞因子的基因潜在激活剂。干扰素诱导的PLSCR1快速生物合成将一些蛋白质靶向细胞核，在那里它与1,4,5-三磷酸肌醇（IP3）受体1型（IP3R1）基因的启动子区域结合并诱导其表达。PLSCR1的棕榈酰化起开关作用，控制其定位于质膜或细胞核内。在本综述中，我们讨论了目前对PLSCR1在其运输、定位和信号功能方面的理解。
