A1 Refereed original research article in a scientific journal

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




AuthorsPeltola KJ, Paukku K, Aho TLT, Ruuska M, Silvennoinen O, Koskinen PJ

PublisherAMER SOC HEMATOLOGY

Publication year2004

JournalBlood

Journal name in sourceBLOOD

Journal acronymBLOOD

Volume103

Issue10

First page 3744

Last page3750

Number of pages7

ISSN0006-4971

DOIhttps://doi.org/10.1182/blood-2003-09-3126


Abstract
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.

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