A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Pim-1 kinase inhibits STAT5-dependent transcription via its interactions with SOCS1 and SOCS3
Tekijät: Peltola KJ, Paukku K, Aho TLT, Ruuska M, Silvennoinen O, Koskinen PJ
Kustantaja: AMER SOC HEMATOLOGY
Julkaisuvuosi: 2004
Journal: Blood
Tietokannassa oleva lehden nimi: BLOOD
Lehden akronyymi: BLOOD
Vuosikerta: 103
Numero: 10
Aloitussivu: 3744
Lopetussivu: 3750
Sivujen määrä: 7
ISSN: 0006-4971
DOI: https://doi.org/10.1182/blood-2003-09-3126
Tiivistelmä
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.
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.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
Turun yliopiston Tutkimustietojärjestelmän portaali