TRANSACTIVATION BY NF-IL6 LAP IS ENHANCED BY PHOSPHORYLATION OF ITS ACTIVATION DOMAIN

ONE of the members of the bZIP family of transcriptional activators1-5 is NF-IL6/LAP (IL-6 DBP, C/EBPbeta, CRP2). NF-IL6/LAP protein is highly expressed in liver nuclei2, where it has been implicated as a master regulator of the acute-phase response1,3,6,7, induced by interleukin-6 (IL-6) and other inflammatory mediators3,8. Also, NF-IL6/LAP is involved in the activation of the IL-6 promoter in response to IL-1 and bacterial lipopolysaccharide1,6. The control of NF-IL6/LAP expression and activity is complex and poorly understood. Under some conditions the NF-IL6/LAP gene is transcriptionally activated by IL-1 and lipopolysaccharide1, whereas in other instances, its binding to cognate DNA sequences is enhanced by cytokines1,3. Additionally, the ability of constitutively expressed NF-IL6/LAP to activate transcription is strongly augmented by IL-6, through an unknown signalling pathway. We now show that stimulation of the protein kinase C pathway increases the phosphorylation of Ser 105 within the activation domain of NF-IL6/LAP, and enhances its transcriptional efficacy.