Kireeva M L, MO F E, Yang G P, Lau L F
Department of Genetics, University of Illinois College of Medicine, Chicago, 60607-7170, USA.
Mol Cell Biol. 1996 Apr;16(4):1326-34. doi: 10.1128/MCB.16.4.1326.
cyr61 was first identified as a growth factor-inducible immediate-early gene in mouse fibroblasts. The encoded Cyr61 protein is a secreted, cystein-rich heparin-binding protein that associates with the cell surface and the extracellular matrix, and in these aspects it resembles the Wnt-1 protein and a number of known growth factors. During embryogenesis, cyr61 is expressed most notably in mesenchymal cells that are differentiating into chondrocytes and in the vessel walls of the developing circulatory system. cyr61 is a member of an emerging gene family that encodes growth regulators, including the connective tissue growth factor and an avian proto-oncoprotein, Nov cyr61 also shares sequence similarities with two Drosophila genes, twisted gastrulation and short gastrulation, which interact with decapentaplegic to regulate dorsal-ventral patterning. In this report we describe the purification of the Cyr61 protein in a biologically active form, and we show that purified Cyr61 has the following activities: (i) it promotes the attachment and spreading of endothelial cells in a manner similar to that of fibronectin; (ii) it enhances the effects of basic fibroblast growth factor and platelet-derived growth factor on the rate of DNA synthesis of fibroblasts and vascular endothelial cells, although it has no detectable mitogenic activity by itself; and (iii) it acts as a chemotactic factor for fibroblasts. Taken together, these activities indicate that Cyr61 is likely to function as an extracellular matrix signaling molecule rather than as a classical growth factor and may regulate processes of cell proliferation, migration, adhesion, and differentiation during development.
Cyr61最初被鉴定为小鼠成纤维细胞中生长因子诱导的即早基因。编码的Cyr61蛋白是一种分泌型、富含半胱氨酸的肝素结合蛋白，它与细胞表面和细胞外基质相关联，在这些方面它类似于Wnt-1蛋白和许多已知的生长因子。在胚胎发生过程中，Cyr61最显著地表达于正在分化为软骨细胞的间充质细胞以及发育中的循环系统的血管壁中。Cyr61是一个新兴基因家族的成员，该家族编码生长调节因子，包括结缔组织生长因子和一种禽类原癌蛋白Nov。Cyr61还与两个果蝇基因twisted gastrulation和short gastrulation具有序列相似性，这两个基因与decapentaplegic相互作用以调节背腹模式形成。在本报告中，我们描述了以生物活性形式纯化Cyr61蛋白的过程，并且我们表明纯化的Cyr61具有以下活性：（i）它以类似于纤连蛋白的方式促进内皮细胞的附着和铺展；（ii）它增强碱性成纤维细胞生长因子和血小板衍生生长因子对成纤维细胞和血管内皮细胞DNA合成速率的影响，尽管它本身没有可检测到的促有丝分裂活性；以及（iii）它作为成纤维细胞的趋化因子。综上所述，这些活性表明Cyr61可能作为细胞外基质信号分子发挥作用，而不是作为经典的生长因子，并且可能在发育过程中调节细胞增殖、迁移、黏附和分化过程。
