IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase.
The biological functions of interleukin-6 (IL-6) are mediated through a signal-transducing component of the IL-6 receptor, gp130, which is associated with the ligand-occupied IL-6 receptor (IL-6R) protein. Binding of IL-6 to IL-6R induced disulfide-linked homodimerization of gp130. Tyrosine kinase activity was associated with dimerized but not monomeric gp130 protein. Substitution of serine for proline residues 656 and 658 in the cytoplasmic motif abolished tyrosine kinase activation and cellular responses but not homodimerization of gp130. The IL-6-induced gp130 homodimer appears to be similar in function to the heterodimer formed between the leukemia inhibitory factor (LIF) receptor (LIFR) and gp130 in response to the LIF or ciliary neurotrophic factor (CNTF). Thus, a general first step in IL-6-related cytokine signaling may be the dimerization of signal-transducing molecules and activation of associated tyrosine kinases.
Institute for Molecular and Cellular Biology, Osaka University, Japan.
M
M
Murakami
M
M
Hibi
N
N
Nakagawa
T
T
Nakagawa
K
K
Yasukawa
K
K
Yamanishi
T
T
Taga
T
T
Kishimoto
D015703:Antigens, CD; D050822:Cytokine Receptor gp130; D004789:Enzyme Activation; D006242:Haptoglobins / Q000096:biosynthesis; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism* / Q000494:pharmacology; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D019947:Receptors, Interleukin-6; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D006242:Haptoglobins; C494199:IL6ST protein, human; D015850:Interleukin-6; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130; D011505:Protein-Tyrosine Kinases