Elzie Carrie Ann, Murphy-Ullrich Joanne E
Department of Pathology, Cell Adhesion and Matrix Research Center, University of Alabama at Birmingham, VH 668, 1530 3rd Avenue South, Birmingham, AL 35294-0019, USA.
Int J Biochem Cell Biol. 2004 Jun;36(6):1090-101. doi: 10.1016/j.biocel.2003.12.012.
Thrombospondin 1 (TSP1) was first recognized as a thrombin-sensitive protein associated with platelet membranes. It is secreted by numerous cell types and its expression is predominant in areas of active tissue remodeling. Thrombospondins 1 and 2 are large, trimeric, matricellular proteins, composed of multiple structural motifs which interact with a diverse array of receptors and molecules. Thrombospondin's capacity to bind multiple receptors renders it multifunctional. The functions of its isolated domains can be overlapping or contradictory. In this review, we focus on the N-terminus of the molecule, first recognized for its strong heparin binding properties and characterized by its susceptibility to proteolytic cleavage from the stalk region of thrombospondin. The N-terminus, called the heparin binding domain (HBD), interacts with a variety of macromolecules including heparan sulfate proteoglycans at the membrane and in the matrix, LDL receptor-related protein (LRP), sulfated glycolipids, calreticulin, and integrins. The HBD mediates endocytosis of thrombospondin. It functions both as a soluble and an insoluble modulator of cell adhesion and motility. In contrast to thrombospondin, the HBD has pro-angiogenic activity. We propose that the HBD of thrombospondins 1 and 2 are found primarily in the cellular microenvironment in conditions of cellular injury, stress and tissue remodeling and that the HBD conveys multiple signals involved in cellular adaptation to injury.
血小板反应蛋白1（TSP1）最初被认为是一种与血小板膜相关的凝血酶敏感蛋白。它由多种细胞类型分泌，其表达在活跃的组织重塑区域中占主导地位。血小板反应蛋白1和2是大型三聚体基质细胞蛋白，由多个结构基序组成，这些基序与多种受体和分子相互作用。血小板反应蛋白结合多种受体的能力使其具有多种功能。其分离结构域的功能可能重叠或相互矛盾。在本综述中，我们关注该分子的N端，它最初因其强大的肝素结合特性而被识别，并以其易从血小板反应蛋白的柄部区域进行蛋白水解切割为特征。N端称为肝素结合结构域（HBD），它与多种大分子相互作用，包括膜上和基质中的硫酸乙酰肝素蛋白聚糖、低密度脂蛋白受体相关蛋白（LRP）、硫酸化糖脂、钙网蛋白和整合素。HBD介导血小板反应蛋白的内吞作用。它既作为细胞粘附和运动的可溶性调节剂，也作为不溶性调节剂发挥作用。与血小板反应蛋白相反，HBD具有促血管生成活性。我们提出，血小板反应蛋白1和2的HBD主要存在于细胞损伤、应激和组织重塑条件下的细胞微环境中，并且HBD传递参与细胞对损伤适应的多种信号。
