PHOSPHORYLATION OF A MYOFIBRILLAR PROTEIN OF MR 150000 IN PERFUSED RAT-HEART, AND THE TENTATIVE IDENTIFICATION OF THIS AS C-PROTEIN
PHOSPHORYLATION OF A MYOFIBRILLAR PROTEIN OF MR 150000 IN PERFUSED RAT-HEART, AND THE TENTATIVE IDENTIFICATION OF THIS AS C-PROTEIN
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DOI：
10.1016/0014-5793(80)80418-2
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发表时间：
1980-01-01
期刊：
影响因子：
3.5
通讯作者：
ENGLAND, PJ
中科院分区：
文献类型：
--
作者：
JEACOCKE, SA;ENGLAND, PJ
在心肌暴露于儿茶酚胺时发生的收缩性增加被认为是由环3 '，5-AMP的细胞内浓度的增加介导的[1，2]。有人提出，这种增加激活了环状3 '，5'-AMP依赖性蛋白激酶，导致膜和肌原纤维蛋白的磷酸化（综述见[3，4]）。许多心肌肌原纤维蛋白的磷酸化已经在体外和体内进行了详细的研究。肌钙蛋白的抑制性亚基（肌钙蛋白-I）可在体外被环AMP依赖性蛋白激酶磷酸化[S，6]，并在灌注心脏中对升高环3 '，5'-AMP的药物产生反应[7，8]。这导致分离的肌原纤维的腺苷三磷酸酶的钙敏感性降低[9，10]和皮肤心脏纤维中的张力发展[11，121]。这可能与用儿茶酚胺处理心肌时观察到的舒张时间缩短有关[3，4]。肌球蛋白的P-轻链在心肌中也被磷酸化，尽管轻链激酶是Ca '+依赖性酶并且不被环AMP激活[13，141]。然而，灌注心脏中P-轻链的磷酸化水平似乎不受儿茶酚胺或增加的Ca*+的影响[15，161]，并且可能不涉及收缩性的短期调节。C-蛋白是一种与横纹肌粗丝中的肌球蛋白相关的蛋白质，分子量为140 000-150 000 [17，18]。在完整肌原纤维上使用C蛋白抗体显示，其位于沿粗丝沿着43 nm的间距处[191. C蛋白会结合各种片段，
The increase in contractility which occurs on exposure of cardiac muscle to catecholamines is thought to be mediated by an increase in the intracellular concentration of cyclic 3’, 5-AMP [1, 2]. It is proposed that this increase activates cyclic 3’, 5’-AMP-dependent protein kinase, resulting in the phosphorylation of membrane and myofibrillar proteins (reviewed in [3, 4]). The phosphorylation of a number of cardiac myofibrillar proteins has been studied in detail both in vitro and in vivo. The inhibitory subunit of troponin (troponin-I) can be phosphorylated in vitro by cyclic AMP-dependent protein kinase [S, 6], and in perfused heart in response to agents which elevate cyclic 3’, 5’-AMP [7, 8]. This results in a decrease in calcium sensitivity of both the adenosine triphosphatase of isolated myofibrils [9, 10] and tension development in skinned cardiac fibres [11, 121. It is possible that this is related to the decrease in relaxation time observed on treatment of cardiac muscle with catecholamines [3, 4]. The P-light chain of myosin is also phosphorylated in cardiac muscle, although the light chain kinase is a Ca’+-dependent enzyme and is not activated by cyclic AMP [13,141. The level of phosphorylation of the P-light chain in perfused hearts does not appear to be affected by catecholamines or increased Ca*+ however [15, 161, and is probably not involved with short-term regulation of contractility.C-protein is a protein of& 140 000-150 000 which is associated with myosin in the thick filaments of striated muscle [17, 18]. Use of antibodies to C-protein on intact myofibrils showed that it was located at a spacing of 43 nm along the thick filament [191. C-protein will bind to various fragments from