title: IL-7 reconstitutes multiple aspects of v-Abl-mediated signaling.
abstract: The mechanism by which early lymphoid cells are selectively transformed by v-Abl is currently unknown. Previous studies have shown constitutive activation of IL-4 and IL-7 signaling pathways, as measured by activation of Janus protein kinase (JAK)1, JAK3, STAT5, and STAT6, in pre-B cells transformed by v-Abl. To determine whether activation of these cytokine signaling pathways by v-Abl is important in the cellular events induced by the Abelson murine leukemia virus, the effects of IL-4 and IL-7 on pre-B cells transformed with a temperature-sensitive v-Abl mutant were examined. Whereas IL-4 had little or no effect, IL-7 delayed both the apoptosis and cell cycle arrest that occur upon v-Abl kinase inactivation. IL-7 also delayed the decreases in the levels of c-Myc, Bcl-2, and Bcl-xL that occur upon loss of v-Abl kinase activity. IL-7 did not maintain v-Abl-mediated differentiation arrest of the pre-B cells, as activation of NF-kappaB and RAG gene transcription was unaffected by IL-7. These results identify a potential role for IL-7 signaling pathways in transformation by v-Abl while demonstrating that a combination of IL-4 and IL-7 signaling cannot substitute for an active v-Abl kinase in transformed pre-B cells.
authors.affiliation: Integrated Program in Cellular, Molecular, and Biophysical Studies, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors.forename: A
authors.initials: A
authors.lastname: Banerjee
authors.forename: P
authors.initials: P
authors.lastname: Rothman
mesh_terms: D000011:Abelson murine leukemia virus / Q000235:genetics / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000166:cytology / Q000821:virology*; D002453:Cell Cycle / Q000187:drug effects; D002472:Cell Transformation, Viral / Q000502:physiology*; D016207:Cytokines / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D016313:Genes, abl; D019254:Genes, bcl-2; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D015847:Interleukin-4 / Q000502:physiology; D015851:Interleukin-7 / Q000494:pharmacology / Q000502:physiology*; D053613:Janus Kinase 1; D053616:Janus Kinase 3; D051379:Mice; D008894:Milk Proteins; D016328:NF-kappa B / Q000378:metabolism; D016374:Oncogene Proteins v-abl / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D050799:STAT5 Transcription Factor; D050800:STAT6 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects*; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D051020:bcl-X Protein
chemical_list: C494811:BCL2L1 protein, human; C494812:Bcl2l1 protein, mouse; D016207:Cytokines; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D015851:Interleukin-7; D008894:Milk Proteins; D016328:NF-kappa B; D016374:Oncogene Proteins v-abl; D019253:Proto-Oncogene Proteins c-bcl-2; D050799:STAT5 Transcription Factor; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D051020:bcl-X Protein; C064658:RAG-1 protein; D015847:Interleukin-4; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507933:JAK3 protein, human; C507905:Jak1 protein, mouse; C507935:Jak3 protein, mouse; D053613:Janus Kinase 1; D053616:Janus Kinase 3