title: Dual retrovirus integration tagging: identification of new signaling molecules Fiz1 and Hipk2 that are involved in the IL-7 signaling pathway in B lymphoblastic lymphomas.
abstract: IL-7R, FLT3, and CD43 are surface antigens expressed during the transition from pro-B to pre-B cells in BM. To understand interactions between their signaling pathways, we analyzed spontaneous mouse B-LBLs with dual MLV integration into Stat5a and Fiz1 or Stat5a and Hipk2. MLV integration resulted in up-regulation of these genes in lymphoma cells compared with normal pro-B cells from the BM. In lymphomas with both integrations into Stat5a and Fiz1, increases in phosphorylated STAT5A and expression of c-Myc, a target gene of STAT5A, were observed following stimulation of the FLT3. Clones with the dual integrations grew faster in IL-7 and FLT3L-supplemented medium than clones with Stat5a integration alone. On the other hand, in lymphomas with integrations into Stat5a and Hipk2, increases in phosphorylated STAT5A and expression of c-Myc were observed following cross-linking of CD43. In conclusion, FLT3 and CD43 signaling pathways involve STAT5A via Fiz1 and Hipk2 in B-LBLs. Identification of the dual MLV integration sites in B-LBLs, therefore, will provide an excellent tool for identification of the signaling pathways in B-LBLs.
authors.affiliation: Department of Forensic Medicine and Molecular Pathology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan. tsuruyam@kuhp.kyoto-u.ac.jp
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Tsuruyama
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Imai
authors.forename: Haruya
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Takuya
authors.initials: T
authors.lastname: Hiratsuka
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Maruyama
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kanaya
authors.forename: Richard
authors.initials: R
authors.lastname: Kaszynski
authors.forename: Guang
authors.initials: G
authors.lastname: Jin
authors.forename: Tomoko
authors.initials: T
authors.lastname: Okuno
authors.forename: Munetaka
authors.initials: M
authors.lastname: Ozeki
authors.forename: Takuro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Takakuwa
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Manabe
authors.forename: Keiji
authors.initials: K
authors.lastname: Tamaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hiai
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D015851:Interleukin-7 / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D009052:Leukemia Virus, Murine / Q000235:genetics*; D051917:Leukosialin / Q000502:physiology; D051379:Mice; D010766:Phosphorylation; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000209:etiology* / Q000276:immunology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D016662:Virus Integration; D051941:fms-Like Tyrosine Kinase 3 / Q000502:physiology
chemical_list: D002352:Carrier Proteins; C120694:Fiz1 protein, mouse; D015851:Interleukin-7; D047908:Intracellular Signaling Peptides and Proteins; D051917:Leukosialin; D050799:STAT5 Transcription Factor; C497863:Spn protein, mouse; C494093:Stat5a protein, mouse; C492003:Hipk2 protein, mouse; C497971:Flt3 protein, mouse; D051941:fms-Like Tyrosine Kinase 3; D017346:Protein Serine-Threonine Kinases