Bursten S L, Locksley R M, Ryan J L, Lovett D H
Medical Service, Seattle Veterans Administration Medical Center-University of Washington 98108.
J Clin Invest. 1988 Nov;82(5):1479-88. doi: 10.1172/JCI113755.
Acylation of cellular proteins with the fatty acids myristate or palmitate represents an important mechanism for the co- or posttranslational modification of proteins. Lipid A, the biologically active component of bacterial endotoxin, exerts a number of biochemical effects on responsive cell types. Evidence is presented that lipid A stimulates the synthesis and subsequent myristyl acylation of intracellular monocyte and glomerular mesangial cell proteins. Two of the myristylated monocyte proteins were identified by specific immunoprecipitation as the 33-kD IL 1 alpha and beta precursors; a similar myristylated protein was found in mesangial cells. The 17-kD secretory form of monocyte IL 1 beta did not contain covalently linked myristate. Myristyl acylation of the IL 1 precursor proteins may facilitate the processing or membrane localization of these proteins, which lack characteristic hydrophobic signal sequences. The acylated 33-kD IL 1 alpha may remain preferentially associated with the membrane in an active form, whereas limited proteolysis may convert the biologically inactive IL 1 beta precursor into the extracellular, nonacylated, active 17-kD protein.
细胞蛋白质被肉豆蔻酸或棕榈酸酰化是蛋白质共翻译或翻译后修饰的一种重要机制。脂多糖A是细菌内毒素的生物活性成分，对反应性细胞类型发挥多种生化作用。有证据表明，脂多糖A刺激细胞内单核细胞和肾小球系膜细胞蛋白质的合成及随后的肉豆蔻酰化。通过特异性免疫沉淀鉴定出两种肉豆蔻酰化的单核细胞蛋白为33-kD白细胞介素1α和β前体；在系膜细胞中也发现了一种类似的肉豆蔻酰化蛋白。单核细胞白细胞介素1β的17-kD分泌形式不含共价连接的肉豆蔻酸。白细胞介素1前体蛋白的肉豆蔻酰化可能有助于这些缺乏特征性疏水信号序列的蛋白的加工或膜定位。酰化的33-kD白细胞介素1α可能以活性形式优先与膜结合，而有限的蛋白水解可能将无生物学活性的白细胞介素1β前体转化为细胞外、非酰化的活性17-kD蛋白。
