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.
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.
Tsuruyama
Tatsuaki
T
Department of Forensic Medicine and Molecular Pathology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan. tsuruyam@kuhp.kyoto-u.ac.jp
Imai
Yukiko
Y
Takeuchi
Haruya
H
Hiratsuka
Takuya
T
Maruyama
Yasuhiro
Y
Kanaya
Kazuya
K
Kaszynski
Richard
R
Jin
Guang
G
Okuno
Tomoko
T
Ozeki
Munetaka
M
Nakamura
Takuro
T
Takakuwa
Tetsuya
T
Manabe
Toshiaki
T
Tamaki
Keiji
K
Hiai
Hiroshi
H
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
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