Bennett C F, Balcarek J M, Varrichio A, Crooke S T
Department of Molecular Pharmacology, Smith Kline & French Laboratories, King of Prussia, Pennsylvania 19406.
Nature. 1988 Jul 21;334(6179):268-70. doi: 10.1038/334268a0.
We report the molecular cloning and sequence of a phosphoinositide-specific phospholipase C (PI-PLC), an enzyme that is of particular interest because of its central role in cell signal transduction. The signals in question are those delivered by hormones to their cell-surface receptors that activate PI-PLC by means of a guanine nucleotide binding protein. Activation of the enzyme leads to the hydrolysis of phosphatidylinositol 4,5-bisphosphate to two second messengers, 1,2-diacylglycerol and inositol 1,4,5-trisphosphate, the second of which ultimately mobilizes internal pools of calcium. There are at least five PI-PLC isoenzymes, whose differences in structure and function are unknown. We have focused on isoenzyme I, which we have recently purified and characterized from guinea pig uterus. We have now determined the sequence of a full length complementary DNA of this isoenzyme from the rat. Although the sequence has little similarity with the only other sequenced PI-PLC isoenzyme, it has a surprising degree of similarity to thioredoxins, protein co-factors in thiol-dependent redox reactions.
我们报道了一种磷酸肌醇特异性磷脂酶C（PI-PLC）的分子克隆及序列，该酶因其在细胞信号转导中的核心作用而备受关注。这里所说的信号是指激素传递给其细胞表面受体的信号，这些受体通过鸟嘌呤核苷酸结合蛋白激活PI-PLC。该酶的激活导致磷脂酰肌醇4,5-二磷酸水解为两种第二信使，即1,2-二酰甘油和肌醇1,4,5-三磷酸，其中后者最终动员细胞内的钙库。至少有五种PI-PLC同工酶，其结构和功能差异尚不清楚。我们重点研究了同工酶I，它是我们最近从豚鼠子宫中纯化并鉴定出来的。我们现已确定了大鼠中该同工酶全长互补DNA的序列。尽管该序列与另一种已测序的PI-PLC同工酶几乎没有相似性，但它与硫氧还蛋白（硫醇依赖性氧化还原反应中的蛋白质辅因子）具有惊人程度的相似性。
