Abstract
Interleukin-6 (IL-6) induces the activation of the Src family kinase Hck, which is associated with the IL-6 receptor beta-chain, gp130. Here we describe the identification of an "acidic" domain comprising amino acids 771 to 811 of gp130 as a binding region for Hck, which mediates proliferative signaling. The deletion of this region of gp130 (i.e., in deletion mutant d771-811) resulted in a significant reduction of Hck kinase activity and cell proliferation upon stimulation of gp130 compared to wild-type gp130. In addition, d771-811 disrupted the growth factor-stimulated activation of Erk and the dephosphorylation of Pyk2. Based on these findings, we propose a novel, acidic domain of gp130, which is responsible for the activation of Hck, Erk, and Pyk2 and signals cell proliferation upon growth factor stimulation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Motifs / physiology
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Animals
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Antigens, CD / genetics
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Antigens, CD / metabolism*
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Cell Division / drug effects
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Cell Division / physiology
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Cell Line
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Cytokine Receptor gp130
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DNA-Binding Proteins / metabolism
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Enzyme Activation / drug effects
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Enzyme Activation / physiology
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Enzyme Inhibitors / pharmacology
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Focal Adhesion Kinase 2
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Growth Substances / pharmacology
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Humans
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Interleukin-6 / metabolism
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Interleukin-6 / pharmacology
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism*
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Mice
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Mitogen-Activated Protein Kinases / metabolism*
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Mutagenesis, Site-Directed
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Protein Binding / drug effects
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Protein Binding / physiology
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Protein Structure, Tertiary / physiology
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Protein-Tyrosine Kinases / metabolism*
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-hck
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Receptors, Erythropoietin / genetics
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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STAT3 Transcription Factor
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Signal Transduction / drug effects
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Signal Transduction / physiology*
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Trans-Activators / metabolism
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Transfection
Substances
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Antigens, CD
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DNA-Binding Proteins
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Enzyme Inhibitors
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Growth Substances
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IL6ST protein, human
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Il6st protein, mouse
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Interleukin-6
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Membrane Glycoproteins
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Proto-Oncogene Proteins
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Receptors, Erythropoietin
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Recombinant Fusion Proteins
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STAT3 Transcription Factor
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STAT3 protein, human
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Stat3 protein, mouse
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Trans-Activators
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Cytokine Receptor gp130
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Protein-Tyrosine Kinases
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Focal Adhesion Kinase 2
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HCK protein, human
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Hck protein, mouse
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Proto-Oncogene Proteins c-hck
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Ptk2b protein, mouse
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Mitogen-Activated Protein Kinases