EXPRESSION OF THE LEUKOCYTE EARLY ACTIVATION ANTIGEN CD69 IS REGULATED BY THE TRANSCRIPTION FACTOR AP-1

The leukocyte Ag CD69, one of the earliest cell surface activation Ags , is up-regulated at the transcriptional level by proinflammatory stim uli involving the NF-kappa B/Rel Family of transcription factors. Howe ver, promoter fragments lacking a critical kappa B motif respond to ot her stimuli such as phorbol esters and triggering Abs against TCR/CD3. Since the 5' promoter flanking region of the CD69 gene contains sever al putative binding sequences for transcription factor activating prot ein-1 (AP-1), we explored its role in the inducible expression of CD69 . Stimuli that induce AP-1, but not NF-kappa B, such as pyrrolidine di thiocarbamate, augmented the cell surface expression of CD69 as well a s its mRNA levels, and the promoter activity of the CD69 gene, This up -regulation is accompanied by an increased binding of jun and fos fami ly members to a consensus AP-1 binding site of the proximal (-16) CD69 promoter region, which seems to be functionally responsive to differe nt activation signals and is transactivated by c-jun expression vector s. Furthermore, cotransfection of a dominant negative version of c-jun , but not I kappa B, abolished the inducible transcriptional activity of the CD69 promoter. In conclusion, the inducible expression of the C D69 gene by mitogenic signals is regulated by the transcription factor AP-1.