Peptide Lv augments L-type voltage-gated calcium channels through vascular endothelial growth factor receptor 2 (VEGFR2) signaling.
Peptide Lv augments L-type voltage-gated calcium channels through vascular endothelial growth factor receptor 2 (VEGFR2) signaling.
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Lv 肽通过血管内皮生长因子受体 2 (VEGFR2) 信号传导增强 L 型电压门控钙通道。
DOI：
10.1016/j.bbamcr.2015.02.007
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Ko,GladysY-P
中科院分区：
文献类型：
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作者：
Shi,Liheng;Ko,Soyoung;Ko,MichaelL;Kim,AndyJeesu;Ko,GladysY-P
我们以前发现了Lv肽，这是一种新的生物活性多肽，可以增强视锥感受器上L类电压门控钙通道(L-VGCC)的活性。在本研究中，我们证实了Lv肽能够增加心肌细胞的L-VGCC电流，并促进内皮细胞的增殖。我们用蛋白质组学的方法确定了Lv肽的特异性受体和结合伙伴，发现血管内皮生长因子受体2(VEGFR2)与Lv肽相互作用。Lv肽可刺激VEGFR2酪氨酸自磷酸化，激活其下游信号转导通路。VEGFR2特异性阻断剂DMH4可阻断Lv多肽的活性，而G蛋白偶联受体的变构抑制剂SCH202676则不能阻断Lv的活性，提示Lv多肽的活性是通过VEGFR2信号途径实现的。抑制VEGFR酪氨酸激酶或其下游信号分子可阻断Lv肽对心肌细胞L-VGCCs的增强作用。此外，Lv肽还能促进培养的人内皮细胞的增殖。通过L-VGCCs的钙内流是心肌细胞兴奋-收缩偶联所必需的。由于Lv肽可通过激活心肌细胞内血管内皮生长因子信号通路增强L-VGCCs，促进血管内皮细胞的增殖，因此Lv肽可能在心血管系统的调节中发挥重要作用。
We previously identified peptide Lv, a novel bioactive peptide that enhances the activity of L-type voltage-gated calcium channels (L-VGCCs) in cone photoreceptors. In this study, we verified that peptide Lv was able to augment L-VGCC currents in cardiomyocytes, as well as promote proliferation of endothelial cells. We used a proteomics approach to determine the specific receptors and binding partners of peptide Lv and found that vascular endothelial growth factor receptor 2 (VEGFR2) interacted with peptide Lv. Peptide Lv treatment in embryonic cardiomyocytes stimulated tyrosine autophosphorylation of VEGFR2 and activated its downstream signaling. Peptide Lv activity was blocked by DMH4, a VEGFR2 specific blocker, but not by SCH202676, an allosteric inhibitor of G protein-coupled receptors, suggesting that the activity of peptide Lv was mediated through VEGFR2 signaling. Inhibition of VEGFR tyrosine kinase or its downstream signaling molecules abolished the augmentation of L-VGCCs elicited by peptide Lv in cardiomyocytes. In addition, peptide Lv promoted cell proliferation of cultured human endothelial cells. Calcium entry through L-VGCCs is essential for excitation–contraction coupling in cardiomyocytes. Since peptide Lv was able to augment L-VGCCs through activation of VEGF signaling in cardiomyocytes and promote proliferation of endothelial cells, peptide Lv may play an important role in regulating the cardiovascular system.