The 9E3/CEF4 cytokine: kinetics of secretion, processing by plasmin, and interaction with extracellular matrix.
The 9E3/CEF4 cytokine: kinetics of secretion, processing by plasmin, and interaction with extracellular matrix.
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9E3/CEF4 细胞因子：分泌动力学、纤溶酶加工以及与细胞外基质的相互作用。
DOI：
10.1006/cyto.1996.0061
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Hanafusa,H
中科院分区：
文献类型：
--
作者：
Martins-Green,M;Stoeckle,M;Hampe,A;Wimberly,S;Hanafusa,H
鸡基因9 E3/CEF 4是一个小的可诱导的细胞因子，与人IL-8和gro α高度同源。它在伤口愈合过程中和劳斯肉瘤病毒诱导的肿瘤周围组织中过表达。9 E3在体内的表达比其他任何小细胞因子都要多，但对其生化特性和功能知之甚少。在这里，我们报告的9 E3基因产物的一些生化特性，蛋白质分泌的动力学，分泌后处理的蛋白质，并在其与ECM分子。蛋白质：（1）在<10分钟内合成和分泌;（2）不被糖基化，并且不以高亲和力结合肝素;（3）以9 kDa形式分泌，并被纤溶酶加工成6-7 kDa形式，纤溶酶是一种在伤口部位释放并与肿瘤相关产生的酶;（4）小的形式结合间质胶原蛋白、层粘连蛋白，并且在较小程度上结合蛋白聚糖，并且不结合IV型胶原蛋白或纤连蛋白。这是迄今为止在真核细胞中描述的最快速分泌的蛋白质，并且是第一个被发现与ECM分子而不是糖胺聚糖相关联的小的可诱导细胞因子。我们的研究结果表明，给予适当的刺激，9 E3细胞因子的水平可以非常迅速地升高，导致类似的快速生物反应。两种形式的分子的不同可用性模式表明，两种亚型可能在体内发挥不同的作用。
The chicken gene, 9E3/CEF4, is a small inducible cytokine highly homologous to human IL-8 andgroα. It is overexpressed during wound healing and in the tissues around tumours induced by Rous sarcoma virus. More is known about the expression of 9E3 in vivo than any other of the small cytokines, yet little is known about its biochemical characteristics and functions. Here we report on some of the biochemical properties of the 9E3 gene product, the kinetics of protein secretion, the post-secretory processing of the protein, and on its association with ECM molecules. The protein: (1) is synthesized and secreted in <10 min; (2) is not glycosylated and does not bind heparin with high affinity; (3) is secreted as a 9 kDa form and is processed to a 6–7 kDa form by plasmin, an enzyme released at wound sites and produced in association with tumours; (4) the small form binds to interstitial collagen, laminin and to a lesser extent to proteoglycan, and does not bind to collagen IV or fibronectin. This is the most rapidly secreted protein yet described in eukaryotic cells and is the first of the small inducible cytokines to be found to associate with ECM molecules other than glycosaminoglycans. Our results suggest that, given the appropriate stimulus, the level of the 9E3 cytokine could be elevated very rapidly, resulting in similarly rapid biological responses. The different modes of availability of the two forms of the molecule suggest that the two isoforms may play different roles in vivo.