Martins-Green M, Stoeckle M, Hampe A, Wimberly S, Hanafusa H
Department of Biology, University of California, Riverside 92521, USA.
Cytokine. 1996 Jun;8(6):448-59. doi: 10.1006/cyto.1996.0061.
The chicken gene, 9E3/CEF4, is a small inducible cytokine highly homologous to human IL-8 and gro alpha. 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.
鸡基因9E3/CEF4是一种小型诱导性细胞因子，与人白细胞介素8（IL-8）和groα高度同源。它在伤口愈合过程中以及劳氏肉瘤病毒诱导的肿瘤周围组织中过度表达。相较于其他小型细胞因子，人们对9E3在体内的表达了解更多，但对其生化特性和功能却知之甚少。在此，我们报告9E3基因产物的一些生化特性、蛋白质分泌动力学、蛋白质分泌后的加工过程以及它与细胞外基质（ECM）分子的关联。该蛋白质：（1）在不到10分钟内合成并分泌；（2）不进行糖基化修饰，也不与肝素高亲和力结合；（3）以9 kDa的形式分泌，被纤溶酶加工成6 - 7 kDa的形式，纤溶酶是一种在伤口部位释放并与肿瘤相关产生的酶；（4）小形式与间质胶原、层粘连蛋白结合，与蛋白聚糖的结合程度较低，不与IV型胶原或纤连蛋白结合。这是真核细胞中迄今描述的分泌速度最快的蛋白质，也是首个被发现与除糖胺聚糖以外的ECM分子相关联的小型诱导性细胞因子。我们的结果表明，在适当刺激下，9E3细胞因子的水平可能会迅速升高，从而导致同样迅速的生物学反应。该分子两种形式的不同存在方式表明这两种异构体在体内可能发挥不同作用。
