Vasodilator-stimulated protein phosphorylation in platelets is mediated by cAMP- and cGMP-dependent protein kinases.
Vasodilator-stimulated protein phosphorylation in platelets is mediated by cAMP- and cGMP-dependent protein kinases.
复制标题
血管舒张剂刺激的血小板蛋白磷酸化是由 cAMP 和 cGMP 依赖性蛋白激酶介导的。
DOI：
--
复制
发表时间：
1987
期刊：
影响因子：
--
通讯作者：
U. Walter
中科院分区：
文献类型：
--
作者：
R. Waldmann;M. Nieberding;U. Walter
血管扩张剂如硝普钠、硝酸甘油和各种前列腺素都能抑制与cGMP或cAMP增加相关的血小板聚集。在我们对完整血小板的研究中，前列腺素E1和硝普钠刺激了几种蛋白质的磷酸化，这些蛋白质可以与已知的由钙调蛋白调节的蛋白激酶或蛋白激酶C磷酸化的蛋白质区分开来。前列腺素E1(10微米)或二丁酰cAMP(2 MM)刺激完整血小板中明显相对分子质量为240,000，68,000，50,000和22,000的蛋白质的磷酸化。这些蛋白质也被低浓度(1-2微米)的cAMP磷酸化。在完整的血小板中，硝普钠(100微米)和cGMP的8-溴衍生物(2 MM)增加了一种MR 50,000蛋白的磷酸化，该蛋白也被低浓度(1-2微米)的cGMP激活。另一种蛋白质(Mr 24000)似乎在完整的血小板中被前列腺素E1和硝普钠以较小程度的程度磷酸化。由于环核苷酸提高剂和环核苷酸类似物都能刺激完整血小板中MR 50 0蛋白的磷酸化，环核苷酸也能刺激血小板膜上MR 5 0 0蛋白的磷酸化，因此对MR 5 0 0蛋白进行了有限蛋白分解、胰酶指纹图谱分析和磷酸氨基酸分析。这些实验表明，硝普钠和前列腺素E1磷酸化的50 kDa蛋白是相同的，两者磷酸化的50 kDa蛋白的多肽也与分别由cGMP和cAMP依赖的蛋白激酶在血小板膜上磷酸化的50 kDa蛋白的多肽相同。CAMP和cGMP依赖的蛋白激酶介导的蛋白磷酸化调节可能是这些能够增加cAMP或cGMP的血管扩张剂抑制血小板聚集的分子机制。
Vasodilators such as sodium nitroprusside, nitroglycerin and various prostaglandins are capable of inhibiting platelet aggregation associated with an increase of either cGMP or cAMP. In our studies with intact platelets, prostaglandin E1 and sodium nitroprusside stimulated the phosphorylation of several proteins which could be distinguished from proteins known to be phosphorylated by a calmodulin-regulated protein kinase or by protein kinase C. Prostaglandin E1 (10 microM) or dibutyryl cAMP (2 mM) stimulated the phosphorylation of proteins with apparent relative molecular masses, Mr, of 240,000, 68,000, 50,000, and 22,000 in intact platelets. These proteins were also phosphorylated in response to low concentrations (1-2 microM) of cAMP in a particulate fraction of platelets. In intact platelets, sodium nitroprusside (100 microM) and the 8-bromo derivative of cGMP (2 mM) increased the phosphorylation of one protein of Mr 50,000 which was also phosphorylated in response to low concentrations (1-2 microM) of cGMP in platelet membranes. An additional protein (Mr 24,000) appeared to be phosphorylated to a lesser degree in intact platelets by prostaglandin E1 and sodium nitroprusside. Since the phosphorylation of the protein of Mr 50,000 was stimulated both in intact platelets by cyclic-nucleotide-elevating agents and cyclic nucleotide analogs, as well as in platelet membranes by cyclic nucleotides, this phosphoprotein was analyzed by limited proteolysis, tryptic fingerprinting and phosphoamino acid analysis. These experiments indicated that the 50-kDa proteins phosphorylated by sodium nitroprusside and prostaglandin E1 were identical, and that the peptide of the 50-kDa protein phosphorylated by both agents was also the same as the peptide derived from the 50-kDa protein phosphorylated in platelet membranes by cGMP- and cAMP-dependent protein kinases, respectively. Regulation of protein phosphorylation mediated by cAMP- and cGMP-dependent protein kinases may be the molecular mechanism by which those vasodilators, capable of increasing either cAMP or cGMP, inhibit platelet aggregation.
影响因子：
56.9
作者：
MAJERUS, PW;CONNOLLY, TM;WILSON, DB
通讯作者：
WILSON, DB
影响因子：
20.3
作者：
B. T. Mellion;L. J. Ignarro;E. H. Ohlstein;E. Pontecorvo;A. Hyman;P. Kadowitz
通讯作者：
B. T. Mellion;L. J. Ignarro;E. H. Ohlstein;E. Pontecorvo;A. Hyman;P. Kadowitz