The Thrombospondins
The Thrombospondins
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DOI：
10.1016/j.biocel.2004.01.004
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发表时间：
2011-10-01
影响因子：
7.2
通讯作者：
Lawler, Jack
中科院分区：
文献类型：
--
作者：
Adams, Josephine C.;Lawler, Jack
血小板反应蛋白-1 （Thrombospondin-1, TSP-1）作为血小板活化后释放的α -颗粒的主要成分和细胞粘附分子在20世纪80年代被研究。1993年，我们发表了一篇简短的综述，讨论了通过分子克隆鉴定出与TSP-1相关的另外四个脊椎动物基因产物[Current Biology 3(1993) 188]。我们对新发现的蛋白质进行了结构分类，并讨论了新基因家族的功能和进化意义。从那时起，关于脊椎动物tsp及其在健康和疾病的细胞和组织中的功能的知识的深度和广度已经扩展到重要的新领域。特别感兴趣的是关于tsp对细胞信号传导和细胞粘附行为的复杂，区域和细胞类型特异性作用的新知识，TSP-1和TSP-2作为抗血管生成剂的作用，TSP-1和TSP-2在伤口愈合中的作用，以及TSP-1， TSP-4和TSP-5/COMP点突变和多态性与人类遗传疾病的关联。TSP家族现在还包括无脊椎动物成员。在本文中，我们给出了2004年对tsp的看法以及我们对仍然存在的重大挑战的看法。本期的其他文章深入讨论了脊椎动物tsp的功能。(C) 2004 Elsevier Ltd.版权所有。血栓反应蛋白是进化上保守的钙结合糖蛋白，可与其他细胞外基质组分进行短暂或长期的相互作用。它们与其他基质分子、细胞因子、接头蛋白和伴侣蛋白具有相同的特性，调节胶原原纤维的组织，并结合和定位一系列生长因子或蛋白酶。在细胞表面，与一系列受体的相互作用激活细胞依赖性信号传导和表型结果。通过这些动态、多效性和环境依赖性的途径，哺乳动物血栓反应蛋白有助于伤口愈合和血管生成、血管壁生物学、结缔组织组织和突触生成。我们概述了区域组织和结构的血栓反应蛋白，其进化的关键特点，和他们的细胞生物学。我们讨论了它们在体内的作用，与人类疾病的关联，以及正在进行的转化应用。在许多方面，我们才刚刚开始认识到这些蛋白质在生理学和病理学中的重要作用。
Thrombospondin-1 (TSP-1) was studied in the 1980s as a major component of platelet alpha-granutes released upon platelet activation and also as a cell adhesion molecule. In 1993, we published a short review that discussed the exciting identification by molecular cloning of four additional vertebrate gene products related to TSP-1 [Current Biology 3 (1993) 188]. We put forward a structurally based classification for the newly identified proteins and discussed the functional and evolutionary implications of the new gene family. Since that time, the depth and breadth of knowledge on vertebrate TSPs and their functions in cells and tissues in health and disease has expanded into important new areas. Of particular interest is the new knowledge on the complex, domain and cell-type specific effects of TSPs on cell-signaling and cell-adhesion behaviour, the roles of TSP-1 and TSP-2 as anti-angiogenic agents, the roles of TSP-1 and TSP-2 in wound-healing, and associations of point mutations and polymorphisms in TSP-1, TSP-4 and TSP-5/COMP with human genetic diseases. The TSP family also now includes invertebrate members. In this article, we give the 2004 view on TSPs and our perspectives on the significant challenges that remain. Other articles in this issue discuss the functions of vertebrate TSPs in depth. (C) 2004 Elsevier Ltd. All rights reserved.Thrombospondins are evolutionarily conserved, calcium-binding glycoproteins that undergo transient or longer-term interactions with other extracellular matrix components. They share properties with other matrix molecules, cytokines, adaptor proteins, and chaperones, modulate the organization of collagen fibrils, and bind and localize an array of growth factors or proteases. At cell surfaces, interactions with an array of receptors activate cell-dependent signaling and phenotypic outcomes. Through these dynamic, pleiotropic, and context-dependent pathways, mammalian thrombospondins contribute to wound healing and angiogenesis, vessel wall biology, connective tissue organization, and synaptogenesis. We overview the domain organization and structure of thrombospondins, key features of their evolution, and their cell biology. We discuss their roles in vivo, associations with human disease, and ongoing translational applications. In many respects, we are only beginning to appreciate the important roles of these proteins in physiology and pathology.