Creatine kinase muscle type specifically interacts with saturated fatty acid- and/or monounsaturated fatty acid-containing phosphatidic acids
Creatine kinase muscle type specifically interacts with saturated fatty acid- and/or monounsaturated fatty acid-containing phosphatidic acids
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DOI：
10.1016/j.bbrc.2019.04.097
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发表时间：
2019-06-11
影响因子：
3.1
通讯作者：
Sakane, Fumio
中科院分区：
文献类型：
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作者：
Hoshino, Fumi;Murakami, Chiaki;Sakane, Fumio
二酰基甘油激酶（DGK）δ是2型糖尿病（T2 D）发病机制中的关键酶，在葡萄糖刺激的成肌细胞中优先产生含饱和脂肪酸（SFA）和/或单不饱和脂肪酸（MUFA）的磷脂酸（PA），如16：0/16：0-PA和16：0/18：1-PA，但不产生含多不饱和脂肪酸（PUFA）的PA。在这里，我们在小鼠骨骼肌中寻找16：0/16：0-PA的靶蛋白，并鉴定了与T2 D相关的能量代谢酶肌酸激酶肌肉型（CKM）。CKM结合到16：0/16：0-PA的最高亲和力（解离常数：2.0 μ M）在所有的PA结合蛋白质迄今报道。有趣的是，CKM优先相互作用与SFA和/或MUFA含有PA，但不与PUFA含有PA。值得注意的是，CKM专门与PA相互作用，而蛋白质不结合其他脂质，如二酰基甘油，磷脂酰丝氨酸，磷脂酰甘油，磷脂酰肌醇，磷脂酰肌醇（3，4，5）-三磷酸和心磷脂。综上所述，这些结果表明，CKM是一种非常独特的PA结合蛋白，其对PA具有极高的亲和力，对SFA/MUFA-PA具有特别的偏好，对PA具有极高的特异性，并表明由DGK δ产生的SFA/MUFA-PA是CKM功能的新型调节剂。(C)2019爱思唯尔公司All rights reserved.
Diacylglycerol kinase (DGK) delta, which is a key enzyme in the pathogenesis of type 2 diabetes (T2D), preferentially generates saturated fatty acid (SFA)- and/or monounsaturated fatty acid (MUFA)-containing phosphatidic acids (PAs) such as 16:0/16:0-PA and 16:0/18:1-PA, but not polyunsaturated fatty acid (PUFA)-containing PAs, in glucose-stimulated myoblast cells. Here, we searched for the target proteins of 16:0/16:0-PA in the mouse skeletal muscle and identified an energy metabolizing enzyme, creatine kinase muscle type (CKM), which is correlated with T2D. CKM bound to 16:0/16:0-PA with the highest affinity (dissociation constant: 2.0 mu M) among all the PA-binding proteins reported thus far. Intriguingly, CKM preferentially interacted with SFA- and/or MUFA-containing PAs, but not with PUFA-containing PAs. Notably, CKM exclusively interacted with PA, whereas the protein did not bind to other lipids such as diacylglycerol, phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, phosphatidylinositol (3,4,5)-trisphosphate and cardiolipin. Taken together, these results demonstrate that CKM is a very unique PA-binding protein that possesses exceedingly high affinity for PA, exceptional preference for SFA/MUFA-PA and extremely high specificity to PA and suggest that SFA/MUFA-PAs produced by DGK delta are novel regulators of CKM function. (C) 2019 Elsevier Inc. All rights reserved.