Thrombopoietin (TPO) induces tyrosine phosphorylation and activation of STAT5 and STAT3

FEBS Letters

Longo, Dan L.²  O'Shea, John J.³  Shimosaka, Akihiro¹  Bacon, Chris M.³  Justin Tortolani, P.³  Rees, Robert C.⁴ 

[1] Kirin Brewing Ltd., Tokyo, Japan;Laboratory of Leukocyte Biology, Biological Response Modifiers Program, NCI-FCRDC, Frederick, MD 21702, USA;Lymphocyte Cell Biology Section, Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Building 10/Room 9N262, National Institutes of Health, Bethesda, MD 20892, USA;Institute for Cancer Studies, University of Sheffield Medical School, Sheffield, South Yorkshire S10 2RX, UK

关键词: Thrombopoietin;    Signal transduction;    Signal transducers and activators of transcription (STAT);    Tyrosine phosphorylation;   

DOI  :  10.1016/0014-5793(95)00796-C

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown