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Blood, 15 May 2004, Vol. 103, No. 10, pp. 3744-3750.
Prepublished online as a Blood First Edition Paper on February 5, 2004; DOI 10.1182/blood-2003-09-3126.

Submitted September 11, 2003
Accepted January 18, 2004
Pim-1 kinase inhibits STAT5-dependent transcription via its interactions with SOCS1 and SOCS3
Katriina J Peltola, Kirsi Paukku, Teija L Aho, Marja Ruuska, Olli Silvennoinen, and Paivi J Koskinen*
Turku Centre for Biotechnology, University of Turku/Abo Akademi University, Turku, Finland; Turku Graduate School of Biomedical Sciences, Turku, Finland
Department of Virology, Haartman Institute, Helsinki, Finland; Programme for Developmental and Reproductive Biology, Biomedicum Helsinki, Helsinki, Finland
Turku Centre for Biotechnology, University of Turku/Abo Akademi University, Turku, Finland
Programme for Developmental and Reproductive Biology, Biomedicum Helsinki, Helsinki, Finland; Institute of Medical Technology, University of Tampere, Tampere, Finland; Deaprtment of Clinical Microbiology, Tampere University Hospital, Tampere, Finland
* Corresponding author; email: paivi.koskinen{at}btk.utu.fi.
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 the SOCS1 and SOCS3 suppressors of cytokine signaling 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.

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