Pim-1 kinase inhibits STAT5-dependent transcription via its interactions with SOCS1 and SOCS3

被引:102
作者
Peltola, KJ
Paukku, K
Aho, TLT
Ruuska, M
Silvennoinen, O
Koskinen, PJ
机构
[1] Univ Turku, Abo Akad Univ, Turku Ctr Biotechnol, FIN-20520 Turku, Finland
[2] Turku Grad Sch Biomed Sci, Turku, Finland
[3] Univ Tampere, Haartman Inst, Dept Virol, FIN-33101 Tampere, Finland
[4] Univ Tampere, Biomedicum Helsinki, Program Dev & Reproduct Biol, FIN-33101 Tampere, Finland
[5] Tampere Univ, Inst Med Technol, FIN-33101 Tampere, Finland
[6] Tampere Univ Hosp, Dept Clin Microbiol, FIN-33521 Tampere, Finland
关键词
D O I
10.1182/blood-2003-09-3126
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Signal transducer and activator of transcription 5 (STAT5) plays a critical role in cytokine-induced survival of hematopoietic cells. One of the STAT5 target genes is pim-1, which encodes an oncogenic serine/threonine kinase. Here we demonstrate that Pim-1 inhibits STAT5-dependent transcription in cells responsive to interleukin-3, prolactin, or erythropoietin. Ectopic expression of Pim-1 in cytokine- dependent FDCP1 myeloid cells results in reduced tyrosine phosphorylation and DNA binding of STAT5, indicating that Pim-1 interferes already with the initial steps of STAT5 activation. However, the Pim-1 kinase does not directly phosphorylate or bind to STAT5. By contrast, Pim-1 interacts with suppressor of cytokine signaling 1 (SOCS1) and SOCS3 and potentiates their inhibitory effects on STAT5, most likely via phosphorylation-mediated stabilization of the SOCS proteins. Thus, both Pim and SOCS family proteins may be components of a negative feedback mechanism that allows STAT5 to attenuate its own activity. (C) 2004 by The American Society of Hematology.
引用
收藏
页码:3744 / 3750
页数:7
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