Induction of mouse β integrin expression following transfection with human α4 chain

✍ Scribed by Deborah L. Webb; Patricia J. Conrad; Lan Ma; Marie-Luise Blue

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 1003 KB
• Volume: 61
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/(sici)1097-4644(19960401)61:1<127::aid-jcb14>3.0.co;2-l

✦ Synopsis

We report here an analysis of the expression and function of the a chain of human VLA-4 in stable mouse L cell transfectants and the requirement for the p chain in these processes. L cells were transfected with human a4 cDNA or a4 and human PI cDNA. Unexpectedly, human a4 cDNA, when transfected alone, could induce de novo surface expression of host p7 and increased expression of host PI. Induction of mouse p7 and pl surface expression was not due to de novo gene activation, but instead represented a4/p intracellular subunit association and transport to the cell surface. Transfection with human p l prevented surface expression of mouse p integrins. Whereas human a4 and human pl subunits associated very tightly in anti-a4 immunoprecipitates, human a4 and mouse p subunits were only partially associated. Furthermore, binding of human/mouse chimeric receptors to recombinant VCAM, a major ligand for a4P7 and a4p1, was very poor, whereas human a4/human PI receptors bound strongly to VCAM. One a4 transfectant, which exhibited a tight human a4/mouse p l association, could be induced, but only after PMA activation, to bind strongly to VCAM. These results indicate that a4 subunits have specific affinity for p7 and P I integrins and require p subunits for surface expression as well as high affinity ligand binding activity. Our results indicate that a tight association between the a4 and p subunit appears to be critical for ligand binding, consistent with a direct as well as regulatory role for the p subunit in ligand binding. Furthermore, these studies demonstrate that expression of foreign recombinant proteins can alter host cell protein expression resulting in de novo surface protein expression.