Identification of Golgi-localized acyl transferases that palmitoylate and regulate endothelial nitric oxide synthase.
Identification of Golgi-localized acyl transferases that palmitoylate and regulate endothelial nitric oxide synthase.
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DOI：
10.1083/jcb.200601051
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发表时间：
2006-07-31
期刊：
影响因子：
--
通讯作者：
Sessa WC
中科院分区：
文献类型：
--
作者：
Fernández-Hernando C;Fukata M;Bernatchez PN;Fukata Y;Lin MI;Bredt DS;Sessa WC
脂质修饰介导许多蛋白质的亚细胞定位和生物活性，包括内皮型一氧化氮合酶（eNOS）。这种酶位于高尔基体的细胞质方面和小窝中，并通过N-肉豆蔻酰化和S-棕榈酰化双重酰化。eNOS的棕榈酰化缺陷突变体释放较少的一氧化氮（NO）。我们确定棕榈酰化eNOS在体内的酶。用eNOS的互补DNA（cDNA）和编码Asp-His-His-Cys基序（DHHC）棕榈酰转移酶家族成员的23个cDNA克隆转染人胚肾293细胞，显示5个克隆（2、3、7、8和21）增强[3 H]-棕榈酸酯掺入eNOS。人内皮细胞表达所有这五种酶，它们与高尔基体和质膜中的eNOS共定位并与eNOS相互作用。重要的是，在人内皮细胞中抑制DHHC-21棕榈酰转移酶而不是DHHC-3会减少eNOS棕榈酰化、eNOS靶向和刺激NO产生。总的来说，我们的数据描述了五个新的高尔基体靶向DHHC酶在人内皮细胞，并建议DHHC-21在管理eNOS的定位和功能的调节作用。
Lipid modifications mediate the subcellular localization and biological activity of many proteins, including endothelial nitric oxide synthase (eNOS). This enzyme resides on the cytoplasmic aspect of the Golgi apparatus and in caveolae and is dually acylated by both N-myristoylation and S-palmitoylation. Palmitoylation-deficient mutants of eNOS release less nitric oxide (NO). We identify enzymes that palmitoylate eNOS in vivo. Transfection of human embryonic kidney 293 cells with the complementary DNA (cDNA) for eNOS and 23 cDNA clones encoding the Asp-His-His-Cys motif (DHHC) palmitoyl transferase family members showed that five clones (2, 3, 7, 8, and 21) enhanced incorporation of [3H]-palmitate into eNOS. Human endothelial cells express all five of these enzymes, which colocalize with eNOS in the Golgi and plasma membrane and interact with eNOS. Importantly, inhibition of DHHC-21 palmitoyl transferase, but not DHHC-3, in human endothelial cells reduces eNOS palmitoylation, eNOS targeting, and stimulated NO production. Collectively, our data describe five new Golgi-targeted DHHC enzymes in human endothelial cells and suggest a regulatory role of DHHC-21 in governing eNOS localization and function.
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影响因子：
4.8
作者：
Lobo, S;Greentree, WK;Deschenes, RJ
通讯作者：
Deschenes, RJ
影响因子：
64.8
作者：
Dimmeler, S;Fleming, I;Zeiher, AM
通讯作者：
Zeiher, AM
DOI：
10.1073/pnas.91.7.2800
发表时间：
1994-03-29
影响因子：
11.1
作者：
MUMBY, SM;KLEUSS, C;GILMAN, AG
通讯作者：
GILMAN, AG
影响因子：
4.8
作者：
Fulton, D;Babbitt, R;Sessa, WC
通讯作者：
Sessa, WC
影响因子：
4.8
作者：
Chaudhary, J;Skinner, MK
通讯作者：
Skinner, MK