Affiliation:
1. From the Turku Centre for Biotechnology, University of Turku/Åbo Akademi University; the Turku Graduate School of Biomedical Sciences; the Haartman Institute, the Department of Virology; the Biomedicum Helsinki, Programme for Developmental and Reproductive Biology; the Institute of Medical Technology, University of Tampere; and the Department of Clinical Microbiology, Tampere University Hospital, Finland.
Abstract
AbstractSignal 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.
Publisher
American Society of Hematology
Subject
Cell Biology,Hematology,Immunology,Biochemistry
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