C. Lutticken et al., INTERLEUKIN-6-INDUCED SERINE PHOSPHORYLATION OF TRANSCRIPTION FACTOR APRF - EVIDENCE FOR A ROLE IN INTERLEUKIN-6 TARGET GENE INDUCTION, FEBS letters, 360(2), 1995, pp. 137-143
The cytokine interleukin-6 (IL-6) rapidly activates a latent cytoplasm
ic transcription factor, acute-phase response factor (APRF), by tyrosi
ne phosphorylation. Activation and DNA binding of APRF are inhibited b
y inhibitors of protein tyrosine kinases but not serine/threonine kina
ses. However, immediate-early gene induction by IL-6 and, as we show h
ere, stimulaton of the promoters of the genes for alpha(2)-macroglobul
in, Jun-B, and intercellular adhesion molecule-1 (ICAM-1) are blocked
by the serine/threonine kinase inhibitor H7. We now show that IL-6 tri
ggers a delayed phosphorylation of APRF at serine resudues which can b
e reversed in vitro by protein phosphatase 2A and is also inhibited by
H7. Therefore, APRF serine phosphorylation is likely to represent a c
rucial event in IL-6 signal transduction leading to target gene induct
ion.