Differential activation of formyl peptide receptor-like 1 by peptide ligands
Differential activation of formyl peptide receptor-like 1 by peptide ligands
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DOI：
10.4049/jimmunol.171.12.6807
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发表时间：
2003-12-15
影响因子：
4.4
通讯作者：
Ryu, SH
中科院分区：
文献类型：
--
作者：
Bae, YS;Yi, HJ;Ryu, SH
甲酰肽受体样1（FPRL 1）在免疫应答的调节中起关键作用。FPRL 1的激活诱导了一种复杂的细胞信号传导模式，这导致了几种免疫应答的调节，例如趋化性迁移和活性氧（ROS）的产生。因为这些细胞应答中的一些对宿主无益，所以选择性调节这些细胞应答的配体是有用的。His-Phe-Tyr-Leu-Pro-Met（HFYLPM）是一种与FPRL 1结合的合成肽。在这项研究中，我们产生了各种HFYLPM类似物，并研究了它们对细胞反应的影响，通过FPRL 1在FPRL 1表达大鼠嗜碱性白血病-2H3细胞或在原代人中性粒细胞。在HXYLPM类似物中，His-Arg-Tyr-Leu-Pro-Met（HRYLPM）激活广谱细胞信号传导事件，包括细胞内Ca 2+浓度增加、磷酸肌醇3-激酶、细胞外信号调节激酶和Akt激活，然而，His-Glu-Tyr-Leu-Pro-Met（HEYLPM）仅激活细胞内Ca 2+浓度和Akt，而不增加Ca 2+。此外，HRYLPM被发现刺激趋化性和活性氧产生通过磷酸肌醇3-激酶和细胞内Ca2+浓度的增加，分别，而HEYLPM刺激趋化性，但没有活性氧产生。关于HRYLPM和HEYLPM差异作用的分子机制，我们发现HRYLPM而不是HEYLPM竞争性抑制I-125标记的Trp-Lys-Tyr-Met-Val-D-Met-NH 2（WKYMVm，FPRL 1配体）与FPRL 1的结合。这项研究表明，重要的化学引诱物受体，FPRL 1，可能是不同的肽配体的差异调制。我们还建议HRYLPM和HEYLPM可用于选择性地调节FPRL 1。
Formyl peptide receptor-like 1 (FPRL1) plays a key role in the regulation of immune responses. The activation of FPRL1 induces a complicated pattern of cellular signaling, which results in the regulation of several immune responses, such as chemotactic migration and the production of reactive oxygen species (ROS). Because some of these cellular responses are not beneficial to the host, ligands that selectively modulate these cellular responses are useful. His-Phe-Tyr-Leu-Pro-Met (HFYLPM) is a synthetic peptide that binds to FPRL1. In this study, we generated various HFYLPM analogues and examined their effects on cellular responses via FPRL1 in FPRL1-expressing rat basophilic leukemia-2H3 cells or in primary human neutrophils. Among the HXYLPM analogues, His-Arg-Tyr-Leu-Pro-Met (HRYLPM) activated a broad spectrum of cellular signaling events, including an intracellular Ca2+ concentration increase, phosphoinositide 3-kinase, extracellular signal-regulated kinase, and Akt activation, however, His-Glu-Tyr-Leu-Pro-Met (HEYLPM) activated only intracellular Ca2+ concentration and Akt but did not increase Ca2+. In addition, HRYLPM was found to stimulate chemotaxis and ROS generation via phosphoinositide 3-kinase and an intracellular Ca2+ concentration increase, respectively, whereas HEYLPM stimulated chemotaxis but not ROS generation. With respect to the molecular mechanisms involved in the differential action of HRYLPM and HEYLPM, we found that HRYLPM but not HEYLPM competitively inhibited the binding of I-125-labeled Trp-Lys-Tyr-Met-Val-D-Met-NH2 (WKYMVm, a FPRL1 ligand) to FPRL1. This study demonstrates that the important chemoattractant receptor, FPRL1, may be differentially modulated by distinct peptide ligands. We also suggest that HRYLPM and HEYLPM may be used to selectively modulate FPRL1.