PDF(Pubmed)
Abstract：
Originally, it was thought that a single serum amyloid A (SAA) protein was involved in amyloid A amyloidosis, but in fact, SAA represents a four-membered family wherein SAA1 and SAA2 are acute phase proteins (A-SAA). SAA is highly conserved throughout evolution within a wide range of animal species suggestive of an important biological function. In fact, A-SAA has been linked to a number of divergent biological activities wherein a number of these functions are mediated via the G protein-coupled receptor (GPCR), formyl peptide receptor (FPR) 2. For instance, through the activation of FPR2, A-SAA has been described to regulate leukocyte activation, atherosclerosis, pathogen recognition, bone formation and cell survival. Moreover, A-SAA is subject to post-translational modification, primarily through proteolytic processing, generating a range of A-SAA-derived peptides. Although very little is known regarding the biological effect of A-SAA-derived peptides, they have been shown to promote neutrophil and monocyte migration through FPR2 activation via synergy with other GPCR ligands namely, the chemokines CXCL8 and CCL3, respectively. Within this review, we provide a detailed analysis of the FPR2-mediated functions of A-SAA. Moreover, we discuss the potential role of A-SAA-derived peptides as allosteric modulators of FPR2.
摘要：
最初,据认为，单一的血清淀粉样蛋白A（SAA）蛋白参与淀粉样蛋白A淀粉样变性，但事实上,SAA代表四元家族,其中SAA1和SAA2是急性期蛋白(A-SAA)。SAA在广泛的动物物种中的整个进化过程中高度保守，表明具有重要的生物学功能。事实上,A-SAA与许多不同的生物学活性有关，其中许多这些功能是通过G蛋白偶联受体（GPCR）介导的。甲酰肽受体(FPR)2.例如,通过激活FPR2，A-SAA已被描述为调节白细胞活化，动脉粥样硬化,病原体识别，骨形成和细胞存活。此外，A-SAA进行翻译后修饰,主要通过蛋白水解加工，产生一系列A-SAA衍生的肽。尽管对A-SAA衍生肽的生物学效应知之甚少，它们已被证明通过与其他GPCR配体的协同作用，通过FPR2激活促进中性粒细胞和单核细胞迁移，即趋化因子CXCL8和CCL3。在这次审查中，我们提供了对A-SAA的FPR2介导的功能的详细分析。此外，我们讨论了A-SAA衍生肽作为FPR2变构调节剂的潜在作用。
