Abstract
Receptor transactivation, i.e., interaction between unrelated receptor systems, is a growing theme in cytokine and growth factor signaling. In this study we reveal for the first time the ability of IFN-alpha to transactivate gp130 in myeloma cells. An epidermal growth factor receptor/gp130 chimeric receptor previously shown by us to transactivate endogenous gp130, provided a complementary tool to study the underlying mechanisms of receptor cross-talk. Further analysis revealed that transactivation of gp130 by IFN-alpha did not require the extracellular or trans-membrane domain of gp130. Moreover, transactivation of gp130 was critically dependent upon Janus kinase activation by the initiating receptor and correlated with rapid and sustained Janus kinase 1 and tyrosine kinase (Tyk) 2 tyrosine phosphorylation. Finally, transactivation of gp130 may be a common theme in myeloma cells, perhaps providing a mechanism for enhanced or qualitatively distinct cellular responses to specific stimuli.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Antigens, CD / genetics*
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Antigens, CD / metabolism*
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Antigens, CD / physiology
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Cell Membrane / genetics
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Cell Membrane / immunology
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Cell Membrane / metabolism
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Cytokine Receptor gp130
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ErbB Receptors / genetics
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ErbB Receptors / physiology
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Extracellular Space / genetics
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Extracellular Space / immunology
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Extracellular Space / metabolism
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Humans
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Interferon-alpha / physiology
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Janus Kinase 1
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Janus Kinase 2
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Ligands
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Membrane Glycoproteins / genetics*
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Membrane Glycoproteins / metabolism*
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Membrane Glycoproteins / physiology
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Multiple Myeloma / immunology*
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Multiple Myeloma / metabolism*
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Phosphorylation
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Protein Structure, Tertiary
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Protein-Tyrosine Kinases / metabolism
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Protein-Tyrosine Kinases / physiology
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Proteins / metabolism
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Proto-Oncogene Proteins*
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Receptor Cross-Talk / immunology
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Receptor, Interferon alpha-beta
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Receptors, Interferon / metabolism
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Receptors, Interferon / physiology
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Receptors, Interleukin-6 / metabolism
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Receptors, Interleukin-6 / physiology
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / physiology
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Signal Transduction / genetics
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Signal Transduction / immunology
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TYK2 Kinase
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Transcriptional Activation* / immunology
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Transfection
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Tumor Cells, Cultured
Substances
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Antigens, CD
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IL6ST protein, human
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Interferon-alpha
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Ligands
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Membrane Glycoproteins
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Proteins
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Proto-Oncogene Proteins
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Receptors, Interferon
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Receptors, Interleukin-6
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Recombinant Fusion Proteins
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Cytokine Receptor gp130
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Receptor, Interferon alpha-beta
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ErbB Receptors
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Protein-Tyrosine Kinases
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JAK1 protein, human
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JAK2 protein, human
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Janus Kinase 1
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Janus Kinase 2
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TYK2 Kinase
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TYK2 protein, human