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

The growth and differentiation of megakaryocytes are regulated by thro mbopoietin (TPO), a recently characterized cytokine which exerts its e ffects via a member of the hematopoietin receptor superfamily, c-Mpl, Since many cytokines which bind hematopoietin receptors activate the S TAT family of transcription factors, we investigated whether STAT prot eins 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 phosphor ylated in response to TPO, Additionally, TPO-induced the tyrosine phos phorylation and DNA-binding activity of STAT3. Together with the recen t demonstration of JAK2 activation in response to TPO, the data presen ted here define a rapid signaling pathway likely to be important in TP O-induced gene regulation.