Identification of a region within the cytoplasmic domain of the interleukin-6 (IL-6) signal transducer gp130 important for ligand-induced endocytosis of the IL-6 receptor

• Published in: The Journal of biological chemistry Vol. 269; no. 29; pp. 19014 - 19020
• Main Authors: DITTRICH, E, ROSE-JOHN, S, GERHARTZ, C, MÜLLBERG, J, STOYAN, T, YASUKAWA, K, HEINRICH, P. C, GRAEVE, L
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 22.07.1994
• Subjects: Amino Acid Sequence; Antigens, CD; Base Sequence; Biological and medical sciences; Cell physiology; Cell receptors; Cell structures and functions; Cytokine Receptor gp130; Cytoplasm - metabolism; Endocytosis; Fundamental and applied biological sciences. Psychology; Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors; In Vitro Techniques; Interleukin-6 - metabolism; Membrane Glycoproteins - chemistry; Membrane Glycoproteins - metabolism; Molecular and cellular biology; Molecular Sequence Data; Oligodeoxyribonucleotides - chemistry; Receptors, Interleukin - metabolism; Receptors, Interleukin-6; Sequence Deletion; Signal Transduction; Structure-Activity Relationship; Interleukin 6; Signal transduction; Endocytosis; Membrane receptor; Transfection; Cytokine; Immunofluorescence; Subunit; Structure function relationship; Aminoacid sequence
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(17)32267-6

Interleukin-6 (IL-6) exerts its action via a cell surface receptor complex consisting of two subunits, the IL-6 receptor and the signal transducer gp130. We have studied the role of both transmembrane proteins for IL-6 internalization and ligand-induced down-regulation of cell surface receptors. Co-expression of wild-type and mutant forms of both the IL-6 receptor and gp130 in transiently transfected COS-7 cells revealed that gp130 is essential for efficient endocytosis and receptor down-regulation. Whereas the cytoplasmic domain of the IL-6 receptor is not significantly involved in the internalization process, deletion of the corresponding domain of gp130 resulted in an almost complete loss of the ability to endocytose IL-6. Mutants with different truncations within the intracellular domain of gp130 revealed that a 10-amino acid sequence TQPLLDSEER is crucial for efficient internalization. Since this sequence contains a putative di-leucine internalization motif, we suggest that a di-leucine motif directs the receptor mediated endocytosis of the IL-6 receptor complex.