THROMBOPOIETIN (TPO) INDUCES TYROSINE PHOSPHORYLATION AND ACTIVATION OF STAT5 AND STAT3

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.