INDUCTION OF MOUSE BETA-INTEGRIN EXPRESSION FOLLOWING TRANSFECTION WITH HUMAN ALPHA-4 CHAIN

We report here an analysis of the expression and function of the alpha chain of human VLA-4 in stable mouse L cell transfectants and the req uirement for the beta chain in these processes. L cells were transfect ed with human alpha 4 cDNA or alpha 4 and human beta 1 cDNA. Unexpecte dly, human alpha 4 cDNA, when transfected alone, could induce de novo surface expression of host beta 7 and increased expression of host bet a 1. Induction of mouse beta 7 and beta 1 surface expression was not d ue to de novo gene activation, but instead represented alpha 4/beta in tracellular subunit association and transport to the cell surface. Tra nsfection with human beta 1 prevented surface expression of mouse beta integrins. Whereas human alpha 4 and human beta 1 subunits associated very tightly in anti-alpha 4 immunoprecipitates, human alpha 4 and mo use beta subunits were only partially associated. Furthermore, binding of human/mouse chimeric receptors to recombinant VCAM, a major ligand for alpha 4 beta 7 and alpha 4 beta 1, was very poor, whereas human a lpha 4/human beta 1 receptors bound strongly to VCAM. One alpha 4 tran sfectant, which exhibited a tight human alpha 4/mouse beta 1 associati on, could be induced, but only after PMA activation, to bind strongly to VCAM. These results indicate that alpha 4 subunits have specific af finity for beta 7 and beta 1 integrins and require beta subunits for s urface expression as well as high affinity ligand binding activity. Ou r results indicate that a tight association between the alpha 4 and be ta subunit appears to be critical for ligand binding, consistent with a direct as well as regulatory role for the beta subunit in ligand bin ding. Furthermore, these studies demonstrate that expression of foreig n recombinant proteins can alter host cell protein expression resultin g in de novo surface protein expression. (C) 1996 Wiley-Liss, Inc.