title: Interleukin 4 signals through two related pathways.
abstract: The interleukin 4 (IL-4) signaling pathway involves activation, by tyrosine phosphorylation, of two distinct substrates, a signal-transducing factor (STF-IL4) and the IL-4-induced phosphotyrosine substrate (4PS). It is not known whether the IL-4-mediated activation of these substrates occurs via related or distinct signaling pathways. We report that 32D cells, an IL-3-dependent myeloid progenitor cell line in which no phosphorylated 4PS is found, activate high levels of STF-IL4 in response to IL-4. Consistent with the known requirement for 4PS or insulin receptor substrate 1 (IRS-1) in IL-4-mediated mitogenesis, activation of STF-IL4 in 32D cells is not sufficient for IL-4-inducible c-myc expression. In addition, we have examined the ability of 32D cells transfected with different truncation mutants of the human IL-4 receptor to activate Jak-3 kinase and STF-IL4 in response to human IL-4. As in the case of 4PS/IRS-1, we have found that activation of both Jak-3 and STF-IL4 requires the presence of the IL-4 receptor region comprising aa 437-557. The finding that the same region of the IL-4 receptor is required for the induction of both 4PS/IRS-1 and STF-IL4 suggests that the IL-4-stimulated activation of these two substrates might involve common factors.
authors.affiliation: Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: A
authors.initials: A
authors.lastname: Pernis
authors.forename: B
authors.initials: B
authors.lastname: Witthuhn
authors.forename: A D
authors.initials: AD
authors.lastname: Keegan
authors.forename: K
authors.initials: K
authors.lastname: Nelms
authors.forename: E
authors.initials: E
authors.lastname: Garfein
authors.forename: J N
authors.initials: JN
authors.lastname: Ihle
authors.forename: W E
authors.initials: WE
authors.lastname: Paul
authors.forename: J H
authors.initials: JH
authors.lastname: Pierce
authors.forename: P
authors.initials: P
authors.lastname: Rothman
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D055313:Cystatin B; D015891:Cystatins / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism; D016259:Genes, myc; D006412:Hematopoietic Stem Cells; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D015847:Interleukin-4 / Q000494:pharmacology*; D053616:Janus Kinase 3; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010750:Phosphoproteins / Q000378:metabolism; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000187:drug effects / Q000502:physiology; D019948:Receptors, Interleukin-4; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000276:immunology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: C524994:CSTB protein, human; D015891:Cystatins; D015853:Cysteine Proteinase Inhibitors; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D015345:Oligonucleotide Probes; D010750:Phosphoproteins; D016271:Proto-Oncogene Proteins c-myc; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D011994:Recombinant Proteins; D015847:Interleukin-4; D019000:Phosphotyrosine; D014443:Tyrosine; D055313:Cystatin B; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3