Open AccessA role for the immunoglobulin‐like domain of the human IL‐6 receptor
Author(s) -
Vollmer Petra,
Oppmann Birgit,
Voltz Nicole,
Fischer Martina,
RoseJohn Stefan
Publication year - 1999
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1327.1999.00511.x
Subject(s) - glycoprotein 130 , transfection , biology , immunoglobulin domain , microbiology and biotechnology , receptor , antibody , cytokine , signal transduction , mutant , biochemistry , immunology , gene , stat3
Interleukin (IL)‐6, IL‐11 and cililary neurotrophic factor (CNTF) belong to the same family of hematopoietic and neurotrophic cytokines. Their receptor complexes contain a cytokine‐binding α receptor and the common glycoprotein (gp)130 subunit for signal transduction. The extracellular parts of the α‐receptor subunits consist of a membrane‐proximal cytokine‐binding domain and an N‐terminal immunoglobulin (Ig)‐like domain with unknown function. We examined the role of the Ig‐like domain of IL‐6R by constructing deletion mutants lacking the Ig domain (IL‐6RΔIg and soluble IL‐6RΔIg). IL‐6RΔIg was shed as effectively as wild‐type IL‐6R from transfected COS‐7 cells upon 4β‐phorbol 12‐myristate 13‐acetate (PMA) treatment, whereas nonstimulated shedding of IL‐6RΔIg was not observed. The shed sIL‐6RΔIg from PMA‐treated cells, as well as the transmembrane IL‐6RΔIg, had the same biological activity as wild‐type sIL‐6R, as measured by the induction of haptoglobin secretion in HepG2‐IL‐6 cells and IL‐6‐dependent proliferation of IL‐6RΔIg transfected BAF/gp130 cells. In COS‐7 cells transfected with IL‐6RΔIg or soluble IL‐6RΔIg cDNA, transport of the deletion mutants through the secretory pathway appeared to be delayed because a sizeable proportion of the mutants was detected as an endo‐β‐ N ‐acetylglucosaminidase‐sensitive intermediate, suggesting that transport and processing of the ΔIg mutants on the secretory pathway were impaired. These experiments suggest that the Ig‐like domain of the IL‐6R is important for intracellular transport of IL‐6R through the secretory pathway. Furthermore, the Ig‐like domain is necessary for noninduced shedding of the IL‐6R, whereas it has no function in PKC‐dependent shedding of the IL‐6R.