G protein‐independent stimulation of human myocardial phospholipase C by mastoparan
G protein‐independent stimulation of human myocardial phospholipase C by mastoparan
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mastoparan 对人心肌磷脂酶 C 的 G 蛋白非依赖性刺激
DOI：
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发表时间：
1997
影响因子：
7.3
通讯作者：
M. Böhm
中科院分区：
文献类型：
--
作者：
P. Schnabel;H. Gäs;T. Nohr;M. Böhm
1磷脂酰肌醇特异性磷脂酶C（PLC）参与许多细胞功能的调节。在心肌中，PLC产生的第二信使在收缩功能的调节和心肌肥大的病理生理学中发挥作用。2在本研究中，在以外源性磷脂为底物的无细胞试验中研究了mastoparan（一种能够通过模拟活化受体的作用来活化异源三聚体G蛋白的十四肽）对膜结合人心肌PLC的影响。3 Mastoparan对人心肌PLC的刺激约为2倍，在约2 μM时具有半数最大效应，在10 μM时具有最大效应。 肽没有改变PLC对游离钙离子的依赖性。为了排除mastoparan由于其两亲性而产生的非特异性作用，使用不同的mastoparan衍生物作为阳性和阴性对照。Mas 17是一种无活性的mastoparan类似物，其物理性质与mastoparan非常相似，但在人心肌膜中不诱导实质性PLC刺激。相比之下，已知活性最高的mastoparan衍生物Mas 7与母体化合物相比引起更明显的PLC活化，表明该作用是序列特异性的。人心肌PLC刺激对百日咳毒素不敏感，并且不能通过添加来自纯化视网膜转导素的过量α亚基或过量GDP或GDPβS来消除。为了研究mastoparan是否通过百日咳毒素不敏感的αq刺激PLC，在COS-1细胞中表达了缺失与αq亚基相互作用位点的PLCβ2缺失突变体。野生型和突变型PLCβ2对mastoparan刺激的敏感性相似。4.提示mastoparan通过不同于异源三聚体G蛋白的机制刺激人心肌PLC。
1 Phosphoinositide‐specific phospholipase C (PLC) is involved in the regulation of many cellular functions. In the myocardium, PLC‐generated second messengers play a role in the regulation of contractile function and in the pathophysiology of myocardial hypertrophy. 2 In the present study, the effect of mastoparan, a tetradecapeptide which is capable of activating heterotrimeric G proteins by mimicking the action of an activated receptor, on membrane‐bound human myocardial PLC, was investigated in a cell‐free assay with exogenous phospholipids as a substrate. 3 Mastoparan stimulated human myocardial PLC approximately two fold with a half‐maximal effect at approximately 2 μM and a maximal effect at 10 μM. The peptide did not alter the dependence of PLC on free calcium ions. In order to exclude non‐specific effects of mastoparan due to its amphiphilic properties, different mastoparan derivatives were used as positive and negative controls. Mas17, an inactive mastoparan analogue with phsyical properties very similar to mastoparan, did not induce substantial PLC stimulation in human myocardial membranes. In contrast, Mas7, the most active mastoparan derivative known, caused a more pronounced PLC activation compared with the mother compound indicating that the effect was sequence‐specific. Human myocardial PLC stimulation was pertussis toxin‐insensitive and could not be abolished by addition of excess α‐subunits from purified retinal transducin or by excess GDP or GDPβS. In order to investigate whether mastoparan stimulated PLC via pertussis toxin‐insensitive αq, a deletion mutant of PLCβ2 deficient of the site of interaction with αq‐subunits was expressed in COS‐1 cells. Both wild‐type and mutant PLCβ2 were similarly sensitive to stimulation by mastoparan. 4 It is concluded that mastoparan stimulates human myocardial PLC by a mechanism distinct from heterotrimeric G proteins.
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乳腺素和其他阳离子肽对 G 蛋白活化的调节。
影响因子：
--
作者：
Ross,EM;Higashijima,T
通讯作者：
Higashijima,T
Mastoparan、相关两亲肽和疏水胺对 Gi 和 Go 的调节。
DOI：
--
发表时间：
1990
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Higashijima,T;Burnier,J;Ross,EM
通讯作者：
Ross,EM
G 蛋白上 Mastoparan 结合位点的图谱。
DOI：
--
发表时间：
1991
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Higashijima,T;Ross,EM
通讯作者：
Ross,EM
黄蜂毒液肽 mastoparan 对从兔脑膜中纯化的磷酸肌醇特异性磷脂酶 C 的影响。
DOI：
10.1016/0005-2760(89)90018-0
发表时间：
1989
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Wallace,MA;Carter,HR
通讯作者：
Carter,HR