The hepatic interleukin‐6 receptor Down‐regulation of the interleukin‐6 binding subunit (gp80) by its ligand

FEBS Letters

Schooltink, Heidi¹  Dittrich, Elke¹  Heinrich, Peter Claus¹  Graeve, Lutz¹  Zohlnhöfer, Dietlind¹  Rose-John, Stefan¹ 

[1] Institut für Biochemie der RWTH Aachen, Pauwelsstr. 30. 5100 Aachen, Germany

关键词: Hepatic IL6-receptor;    Interleukin-6;    Internalization;    Down-regulation;    Signal transduction;    IL6;    interleukin-6;    rh;    recombinant human;    IL6R;    interleukin-6 receptor;   

DOI  :  10.1016/0014-5793(92)81004-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Interleukin-6 (IL6) exerts its action via a cell surface receptor composed of an 80 kDa IL6-binding protein (gp80) and a 130 kDa polypeptide involved in signal transduction (gp13O). We studied the role of gp80 in binding, internalization and down-regulation of the hepatic IL6-receptor (IL6R) by its ligand in human hepatoma cells (HepG2). Comparison of transfected HepG2 cells overexpressing gp8O with parental cells indicate that gp80 is responsible for low affinity binding (K _d = 500 pM) of IL6. Furthermore, gp80 is rate-limiting in internalization and degradation of IL6. Internalization resulted in a rapid down-regulation (t ≈ 15–30 min) of IL6-binding sites at the cell surface. More than 80% of the internalized [¹²⁵I]rhIL6 was degraded. The reappearance of IL6-binding sites at the cell surface required >8 h and was sensitive to cycloheximide, suggesting that gp80 is not recycled after internalization. The down-regulation of the hepatic IL6R by its ligand might play an important role as a protection against overstimulation.

【 授权许可】

Unknown