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β1整合素功能的调控。刺激性表位的定位。

Control of beta1 integrin function. Localization of stimulatory epitopes.

作者信息

Wilkins J A, Li A, Ni H, Stupack D G, Shen C

机构信息

Rheumatic Disease Unit Research Laboratory, Department of Internal Medicine, University of Manitoba, Winnipeg MB R3A 1M4, Canada.

出版信息

J Biol Chem. 1996 Feb 9;271(6):3046-51.

PMID:8621699
Abstract

The beta1 integrins can be expressed on the surface of cells in a latent form, which is activated by a variety of stimuli. As an approach to examining the transition to an active receptor, a panel of stimulatory antibodies to beta1 were produced and characterized. These antibodies induced adherence of the T-leukemic cell line Jurkat to collagen and fibronectin. Competitive antibody binding assays indicated the existence of at least three distinct epitope clusters A (B3B11, JB1B, 21C8), B (B44, 13B9), and C(N29) defined by the indicated antibodies. Two antibodies to the A site, JB1B and B3B11, were shown to localize to positions 671-703 and 657-670, respectively, of the beta1. This region is located in an area encompassing a predicted disulfide bond between linearly distant cysteines in beta1 (Cys415-Cys671). The homologous region of the beta3 integrin (490 690 and 602 690) has been shown to be one of the sites recognized by stimulatory antibodies to ligand-induced binding sites. The present results indicate the existence of multiple stimulatory regions and suggest considerable homology between the locations of beta1 and beta3 regulatory sites.

摘要

β1整合素可以以潜在形式表达在细胞表面,其可被多种刺激激活。作为研究向活性受体转变的一种方法,制备并鉴定了一组针对β1的刺激抗体。这些抗体诱导T白血病细胞系Jurkat黏附于胶原蛋白和纤连蛋白。竞争性抗体结合试验表明存在至少三个由所示抗体定义的不同表位簇A(B3B11、JB1B、21C8)、B(B44、13B9)和C(N29)。针对A位点的两种抗体JB1B和B3B11分别定位于β1的671 - 703位和657 - 670位。该区域位于β1中线性距离较远的半胱氨酸(Cys415 - Cys671)之间预测的二硫键所在区域。β3整合素的同源区域(490 - 690和602 - 690)已被证明是配体诱导结合位点的刺激抗体识别的位点之一。目前的结果表明存在多个刺激区域,并提示β1和β3调节位点的位置之间存在相当大的同源性。

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