Transactivation of gp130 in myeloma cells.
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.
French
Jena D
JD
Department of Immunology, Mayo Graduate and Medical Schools, Mayo Clinic, Rochester, MN 55905, USA.
Walters
Denise K
DK
Jelinek
Diane F
DF
D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D002462:Cell Membrane / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D050822:Cytokine Receptor gp130; D066246:ErbB Receptors / Q000235:genetics / Q000502:physiology; D005110:Extracellular Space / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000502:physiology; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D008024:Ligands; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D009101:Multiple Myeloma / Q000276:immunology* / Q000378:metabolism*; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000378:metabolism / Q000502:physiology; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D020239:Receptor Cross-Talk / Q000276:immunology; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000378:metabolism / Q000502:physiology; D019947:Receptors, Interleukin-6 / Q000378:metabolism / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D053634:TYK2 Kinase; D015533:Transcriptional Activation / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; C494199:IL6ST protein, human; D016898:Interferon-alpha; D008024:Ligands; D008562:Membrane Glycoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D017471:Receptors, Interferon; D019947:Receptors, Interleukin-6; D011993:Recombinant Fusion Proteins; D050822:Cytokine Receptor gp130; D053633:Receptor, Interferon alpha-beta; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507924:JAK2 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D053634:TYK2 Kinase; C070139:TYK2 protein, human