NEW PERSPECTIVES IN CELL-ADHESION - RGD AND INTEGRINS

NEW PERSPECTIVES IN CELL-ADHESION - RGD AND INTEGRINS
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DOI:
10.1126/science.2821619
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发表时间:
1987-10-23
期刊:
影响因子:
56.9
通讯作者:
PIERSCHBACHER, MD
PIERSCHBACHER, MD
中科院分区:
综合性期刊1区
文献类型:
--
作者:
RUOSLAHTI, E;PIERSCHBACHER, MD

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在理解导致细胞粘附的分子相互作用方面取得了快速进展。存在于细胞外基质和血液中的许多粘附蛋白含有三肽精氨酸-甘氨酸-天冬氨酸(RGD)作为其细胞识别位点。这些蛋白质包括纤连蛋白、玻连蛋白、骨桥蛋白、胶原蛋白、血小板反应蛋白、纤维蛋白原和血管性血友病因子。每种粘附蛋白的RGD序列被结构相关受体整合素家族的至少一个成员识别,整合素是具有两个跨膜亚基的异二聚体蛋白。这些受体中的一些仅与单个粘附蛋白的RGD序列结合,而另一些则识别它们的组。单个蛋白质中的RGD序列的构象可能对这种识别特异性至关重要。在质膜的细胞质侧,受体将细胞外基质连接到细胞骨架。已经鉴定了十种以上证实或怀疑含有RGD的粘附促进蛋白,并且整合素家族包括至少同样多的识别这些蛋白的受体。粘附蛋白及其受体共同构成了一个多功能的识别系统,为细胞提供锚定、迁移牵引以及极性、位置、分化和可能的生长信号。
Rapid progress has been made in the understanding of the molecular interactions that result in cell adhesion. Many adhesive proteins present in extracellular matrices and in the blood contain the tripeptide arginine-glycine-aspartic acid (RGD) as their cell recognition site. These proteins include fibronectin, vitronectin, osteopontin, collagens, thrombospondin, fibrinogen, and von Willebrand factor. The RGD sequences of each of the adhesive proteins are recognized by at least one member of a family of structurally related receptors, integrins, which are heterodimeric proteins with two membrane-spanning subunits. Some of these receptors bind to the RGD sequence of a single adhesion protein only, whereas others recognize groups of them. The conformation of the RGD sequence in the individual proteins may be critical to this recognition specificity. On the cytoplasmic side of the plasma membrane, the receptors connect the extracellular matrix to the cytoskeleton. More than ten proved or suspected RGD-containing adhesion-promoting proteins have already been identified, and the integrin family includes at least as many receptors recognizing these proteins. Together, the adhesion proteins and their receptors constitute a versatile recognition system providing cells with anchorage, traction for migration, and signals for polarity, position, differentiation, and possibly growth.