Interleukin‐6‐induced serine phosphorylation of transcription factor APRF: evidence for a role in interleukin‐6 target gene induction

FEBS Letters

Lütticken, Claudia²  Yuan, Juping²  Kruijer, Wiebe⁴  Schindler, Chris¹  Caldenhoven, Eric³  Schwartz, Claudia²  Horn, Friedemann²  Heinrich, Peter C²  Coffer, Paul³ 

[1] Division of Molecular Medicine, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA;Institut für Biochemie der Rheinisch-Westfälischen Technischen Hochschule Aachen, Pauwelsstrasse 30, D-52057 Aachen, Germany;Hubrecht Laboratorium, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands;Department of Genetics, University of Groningen, PO Box 14, 9750 AA Haren, The Netherlands

关键词: Interleukin-6;    Signal transduction;    Transcription factor;    Acute-phase response factor;    Stat;    Phosphorylation;    APRF;    acute-phase response factor;    CAT;    chloramphenicol acetyltransferase;    H7;    1-(5-isoquinolinesulfonyl)-2-methylpiperazine;    ICAM-1;    intercellular adhesion molecule 1;    IL-6;    interleukin-6;    IL-6RE;    IL-6 response element;   

DOI  :  10.1016/0014-5793(95)00076-L

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The cytokine interleukin-6 (IL-6) rapidly activates a latent cytoplasmic transcription factor, acute-phase response factor (APRF), by tyrosine phosphorylation. Activation and DNA binding of APRF are inhibited by inhibitors of protein tyrosine kinases but not serine/threonine kinases. However, immediate-early gene induction by IL-6 and, as we show here, stimulation of the promoters of the genes for α ₂-macroglobulin, Jun-B, and intercellular adhesion molecule-1 (ICAM-1) are blocked by the serine/threonine kinase inhibitor H7. We now show that IL-6 triggers a delayed phosphorylation of APRF at serine resudues which can be reversed in vitro by protein phosphatase 2A and is also inhibited by H7. Therefore, APRF serine phosphorylation is likely to represent a crucial event in IL-6 signal transduction leading to target gene induction.

【 授权许可】

Unknown