CDB15:0000917 IL6 — IL6R

ABSTRACT: All cytokines belonging to the interleukin-6 (IL-6)-type family of cytokines utilize receptors that have a modular build of several immunoglobulin-like and fibronectin type III-like domains. Characteristic of these receptors is a cytokine receptor homology region consisting of two such fibronectin domains defined by a set of four conserved cysteines and a tryptophan-serine-X-tryptophan-serine sequence motif. On target cells, interleukin-6 first binds to its specific receptor and subsequently to a homodimer of the signal transducer protein gp130. The interleukin-6 receptor consists of three extracellular domains. The N-terminal immunoglobulin-like domain is not involved in ligand binding, whereas the third membrane proximal fibronectin-like domain accounts for more than 90% of the binding energy to IL-6. Here, the key residues of this fibronectin-like domain involved in the interaction with IL-6 are described. Chemical shift mapping data with 15N-labeled IL-6R-D3 and unlabeled IL-6 coupled with recent structural data clearly reveal the epitope within the IL-6R-D3 responsible for mediating the high affinity interaction with its cognate cytokine.

ABSTRACT: Interleukin-6 (IL-6/BSF-2/IFN beta 2) is a multifunctional cytokine that regulates the growth and differentiation of various tissues, and is known particularly for its role in the immune response and acute phase reactions. A complementary DNA encoding the human IL-6 receptor (IL-6-R) has now been isolated. The IL-6-R consists of 468 amino acids, including a signal peptide of approximately 19 amino acids and a domain of approximately 90 amino acids that is similar to a domain in the immunoglobulin (Ig) superfamily. The cytoplasmic domain of approximately 82 amino acids lacks a tyrosine/kinase domain, unlike other growth factor receptors.