Threonine-5 at the N-terminus can modulate sarcolipin function in cardiac myocytes.
Threonine-5 at the N-terminus can modulate sarcolipin function in cardiac myocytes.
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N 末端的苏氨酸-5 可以调节心肌细胞中的肌磷脂功能。
DOI：
10.1016/j.yjmcc.2009.07.014
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发表时间：
2009-11
影响因子：
5
通讯作者：
Periasamy M
中科院分区：
文献类型：
--
作者：
Bhupathy P;Babu GJ;Ito M;Periasamy M
肌磷脂（Sarcolipin，SLN）是心房肌浆网（SR）钙转运的重要调节因子。SLN对心肌肌浆网Ca ~（2+）ATP酶（SERCA）泵的抑制作用可被β-肾上腺素能刺激所解除，表明SLN是一种可逆性抑制剂。然而，SLN对SERCA泵的可逆调节机制尚未确定。在目前的研究中，使用成年大鼠心室肌细胞，我们提供的证据表明，苏氨酸5（T5）在N-末端的SLN，这是保守的不同物种之间的残基，严格调节SLN的功能。点突变T5→丙氨酸对心肌细胞收缩力和钙瞬变的抑制作用与野生型SLN相似，而点突变T5→谷氨酸模拟磷酸化则取消了SLN的抑制作用。我们的研究结果表明，T5可以在体外被钙-钙调蛋白依赖性蛋白激酶II（CaMKII）磷酸化。用autocamtide抑制肽阻断过表达WT-SLN的心肌细胞中的CaMK II活性完全消除β-肾上腺素能反应。综上所述，我们的数据表明，T5是通过CaMKII途径通过磷酸化/去磷酸化机制调节SLN功能的关键氨基酸。
Sarcolipin (SLN) has emerged as an important regulator of the atrial sarcoplasmic reticulum (SR) Ca2+ transport. The inhibitory effect of SLN on cardiac SR Ca2+ ATPase (SERCA) pump can be relieved by β-adrenergic stimulation, which indicates that SLN is a reversible inhibitor. However, the mechanism of this reversible regulation of SERCA pump by SLN is yet to be determined. In the current study using adult rat ventricular myocytes we provide evidence that the threonine 5 (T5) residue at the N-terminus of SLN which is conserved among various species, critically regulates the SLN function. Point mutation of T5→alanine exerts an inhibitory effect on myocyte contractility and calcium transients similar to that of wild-type SLN, whereas mutation of T5→glutamic acid which mimics the phosphorylation abolished the inhibitory function of SLN. Our results showed that T5 can be phosphorylated in vitro by calcium–calmodulin dependent protein kinase II (CaMKII). Blocking the CaMKII activity in WT-SLN overexpressing myocytes using autocamtide inhibitory peptide completely abolished the β-adrenergic response. Taken together, our data suggest that T5 is the key amino acid which modulates SLN function via phosphorylation/dephosphorylation mechanisms through CaMKII pathway.
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影响因子：
4.8
作者：
Odermatt, A;Becker, S;MacLennan, DH
通讯作者：
MacLennan, DH
影响因子：
9.3
作者：
Klein, AL;Wold, LE;Ren, J
通讯作者：
Ren, J
影响因子：
5
作者：
Kadambi, VJ;Koss, KL;Kranias, EG
通讯作者：
Kranias, EG
影响因子：
20.1
作者：
KOSS, KL;PONNIAH, S;KRANIAS, EG
通讯作者：
KRANIAS, EG
DOI：
10.1111/j.1749-6632.2003.tb07231.x
发表时间：
2003-01-01
期刊：
NA,K-ATPASE AND RELATED CATION PUMPS
影响因子：
--
作者：
MacLennan, DH;Asahi, M;Tupling, AR
通讯作者：
Tupling, AR