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.
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.
Dittrich
E
E
Institute of Biochemistry, Rheinisch-Westfälische Technische Hochschule Aachen, Germany.
Rose-John
S
S
Gerhartz
C
C
Müllberg
J
J
Stoyan
T
T
Yasukawa
K
K
Heinrich
P C
PC
Graeve
L
L
D000595:Amino Acid Sequence; D015703:Antigens, CD; D001483:Base Sequence; D050822:Cytokine Receptor gp130; D003593:Cytoplasm / Q000378:metabolism; D004705:Endocytosis; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D018123:Receptors, Interleukin / Q000378:metabolism*; D019947:Receptors, Interleukin-6; D017384:Sequence Deletion; D015398:Signal Transduction; D013329:Structure-Activity Relationship
D015703:Antigens, CD; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130