Comparison of IL-13- and IL-4-induced signaling in EBV-immortalized human B cells.
Interleukin 4 (IL-4) and Interleukin 13 (IL-13) have been shown to have numerous similar effects on human B cells; however, the mechanism of signal transduction is not known. We have examined IL-4- and IL-13-induced signal transduction in Epstein-Barr virus (EBV)-immortalized B cells. We demonstrate that Janus kinase 3 (JAK3) and Tyk2 but not JAK1 and JAK2 tyrosine kinases were constitutively phosphorylated in three EBV B cell lines. The phosphorylation level of Tyk2 was augmented at a low level in response to IL-13 and IL-4 in two of three cell lines; however, IL-13 did not induce or augment phosphorylation of the other JAK kinases. On the other hand, IL-4 further augmented phosphorylation of JAK3 and induced the phosphorylation of JAK1 kinases. IL-4 receptor p140 protein was also constitutively phosphorylated in two of three EBV B cell lines examined and both IL-4 and IL-13 further augmented its phosphorylation. Insulin receptor substrate (IRS)-1 or IRS-2 proteins were not constitutively phosphorylated nor did IL-13 and IL-4 induce phosphorylation of these proteins. In contrast to JAKs, IL-4-specific signal transducer and activator of transcription (STAT6) was not constitutively phosphorylated or activated in these cell lines, but both IL-4 and IL-13 induced their phosphorylation and activation. These findings suggest that in EBV-immortalized B cells JAK3 and Tyk2 proteins were constitutively phosphorylated but STAT6 protein was not constitutively phosphorylated. In addition, despite major similarities in biological effects between IL-4 and IL-13, phosphorylation patterns of JAK kinases in response to IL-13 in EBV-immortalized B cells appear to be different from those of IL-4.
Murata
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Laboratory of Molecular Tumor Biology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.
Puri
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D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D019556:COS Cells; D002460:Cell Line; D002472:Cell Transformation, Viral; D015342:DNA Probes / Q000235:genetics; D004854:Herpesvirus 4, Human; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D018793:Interleukin-13 / Q000494:pharmacology* / Q000502:physiology; D015847:Interleukin-4 / Q000494:pharmacology* / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D053616:Janus Kinase 3; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D019948:Receptors, Interleukin-4; D050800:STAT6 Transcription Factor; D015398:Signal Transduction; D053634:TYK2 Kinase; D015534:Trans-Activators / Q000378:metabolism
D015703:Antigens, CD; D015342:DNA Probes; C526292:IRS1 protein, human; C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins; D018793:Interleukin-13; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D011506:Proteins; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators; D015847:Interleukin-4; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3; D053634:TYK2 Kinase; C070139:TYK2 protein, human