title: Thrombopoietin (TPO) induces tyrosine phosphorylation and activation of STAT5 and STAT3.
abstract: The growth and differentiation of megakaryocytes are regulated by thrombopoietin (TPO), a recently characterized cytokine which exerts its effects via a member of the hematopoietin receptor superfamily, c-Mpl. Since many cytokines which bind hematopoietin receptors activate the STAT family of transcription factors, we investigated whether STAT proteins were activated by TPO. TPO induced the formation of a DNA-binding complex recognizing a known STAT-binding sequence. STAT5 was a major component of this DNA-binding complex, and STAT5 was tyrosine phosphorylated in response to TPO. Additionally, TPO-induced the tyrosine phosphorylation and DNA-binding activity of STAT3. Together with the recent demonstration of JAK2 activation in response to TPO, the data presented here define a rapid signaling pathway likely to be important in TPO-induced gene regulation.
authors.affiliation: Lymphocyte Cell Biology Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Bacon
authors.forename: P J
authors.initials: PJ
authors.lastname: Tortolani
authors.forename: A
authors.initials: A
authors.lastname: Shimosaka
authors.forename: R C
authors.initials: RC
authors.lastname: Rees
authors.forename: D L
authors.initials: DL
authors.lastname: Longo
authors.forename: J J
authors.initials: JJ
authors.lastname: O'Shea
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D053614:Janus Kinase 2; D007947:Leukemia, Megakaryoblastic, Acute; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008894:Milk Proteins; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010766:Phosphorylation; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins / Q000494:pharmacology; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D013926:Thrombopoietin / Q000494:pharmacology*; D015534:Trans-Activators / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D016207:Cytokines; D004268:DNA-Binding Proteins; D008894:Milk Proteins; D009838:Oligodeoxyribonucleotides; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D019000:Phosphotyrosine; D014443:Tyrosine; D013926:Thrombopoietin; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2