THE 9E3 CEF4 CYTOKINE - KINETICS OF SECRETION, PROCESSING BY PLASMIN,AND INTERACTION WITH EXTRACELLULAR-MATRIX/

The chicken gene, 9E3/CEF4, is a small inducible cytokine highly homol ogous to human IL-8 and gro alpha, It is overexpressed during wound he aling 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 t he small cytokines, yet little is known about its biochemical characte ristics and functions, Here we report on some of the biochemical prope rties 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 mi n; (2) is not glycosylated and does not bind heparin with high affinit y; (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 associat ion with tumours; (4) the small form binds to interstitial collagen, l aminin and to a lesser extent to proteoglycan, and does not bind to co llagen TV or fibronectin, This is the most rapidly secreted protein ye t described in eukaryotic cells and is the first of the small inducibl e cytokines to be found to associate with ECM molecules other than gly cosaminoglycans, Our results suggest that, given the appropriate stimu lus, the level of the 9E3 cytokine could be elevated very rapidly, res ulting in similarly rapid biological responses, The different modes of availability of the two forms of the molecule suggest that the two is oforms may play different roles in vivo. (C) 1996 Academic Press Limit ed