EXTRACELLULAR-MATRIX - THE THROMBOSPONDIN FAMILY
EXTRACELLULAR-MATRIX - THE THROMBOSPONDIN FAMILY
复制标题
DOI：
10.1016/0960-9822(93)90270-x
复制
发表时间：
1993-03-01
期刊：
影响因子：
9.2
通讯作者：
LAWLER, J
中科院分区：
文献类型：
--
作者：
ADAMS, J;LAWLER, J
近年来，人们对纤维连接蛋白和层粘连蛋白等细胞外基质糖蛋白在调节细胞行为、增殖和分化中的作用有了新的认识。这在一定程度上是因为人们对这些糖蛋白与细胞相互作用的分子机制有了更好的理解。与此同时，其他基质分子的可能功能仍然不太清楚。凝血酶敏感蛋白是细胞外基质中的一种糖蛋白，最初是从凝血酶刺激的血小板的u颗粒中释放出来的420k~3聚体分子。现已清楚的是，凝血酶敏感蛋白存在于发育和修复组织的细胞外基质中，并且在体外具有黏附和促进生长的活性，这些性质表明凝血酶敏感蛋白可能是一种促进细胞运动的独特基质成分。目前研究的重点之一是确定凝血酶反应蛋白的细胞结合部位和特异性受体[1，2]。最近发现的一系列血栓反应蛋白相关蛋白增加了这一努力的动力，并迫使重新评估血栓反应蛋白在细胞外基质中的作用。对第一种被识别的形式的血栓反应蛋白(现在称为TSP-1)的分子克隆显示，该三聚体的每个亚单位由多个结构域组成：氨基：；和羧基末端球状结构域，一个与前胶原相似的序列区域，以及三种类型的重复序列基序，命名为类型1，类型2和类型3重复(图1)。类型1重复序列具有不同细胞类型的连接位点，类型2重复序列类似于表皮生长因子(EGF)中的重复序列，类型3重复序列形成一系列的钙结合环。在过去的一年里，已经鉴定出四种具有结构的蛋白质？~；
Recent years have witnessed a new appreciation of the roles of extracellular matrix glycoproteins, such as fibronectin and laminin, in regulating cell behavior, prolif eration and differentiation. This has come about, in part, through an improved understanding of the molecular mechanisms by which these glycoproteins interact with cells. Meanwhile, the possible functions of other matrix molecules remain less well understood. Thrombospondin is a glycoprotein of the extracellular matrix that was first isolated as a 420 k~, trimeric molecule released from the u-granules of thrombin-stimulated platelets. It has since become clear that thrombospondin is present in the extracellular matrix of developing and repairing tissue and that it has adhesive and growth-promoting activities in vitro Taken together, these properties su% cst that thrombospondin may be a unique matrix component that facilitates cell movement. One focus of current research is the identification of cellular binding sites and specific receptors for thrombospondin [1, 2]. The recent discovery of a family of thrombospondin-related proteins has added impetus to this endeavour, and forces a reappraisal of the roles attributed to thrombospondin in the the extracellular matrix.Molecular cloning of the first identilied form of thrombospondin (now called TSP-1) revealed that each subunit of the trimer consists of multiple domains: amino-:; ad carboxy-terminal globular domains, a region of sequei EX similarity to procollagen, and three types of repeated XI-quence motifs, designated type 1, type 2 and type 3 repeats (Fig. 1). The type 1 repeats have attachment sites for various cell types, type 2 repeats resemble repeats in epidermal growth factor (EGF) and type 3 repeats form a series of Ca2+-binding loops.! A the past year, four proteins have been identified that are structural?~;