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

THROMBOPOIETIN (TPO) INDUCES TYROSINE PHOSPHORYLATION AND ACTIVATION OF STAT5 AND STAT3
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DOI:
10.1016/0014-5793(95)00796-c
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发表时间:
1995-08-14
期刊:
影响因子:
3.5
通讯作者:
OSHEA, JJ
OSHEA, JJ
中科院分区:
生物学3区
文献类型:
--
作者:
BACON, CM;TORTOLANI, PJ;OSHEA, JJ

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巨核细胞的生长和分化受血小板生成素(TPO)调控,TPO是一种新发现的细胞因子,通过造血生成素受体超家族成员c-Mpl发挥其作用。由于许多结合造血生成素受体的细胞因子激活STAT家族的转录因子,我们研究了STAT蛋白是否被TPO激活,TPO诱导形成识别已知STAT结合序列的dna结合复合体。STAT5是该dna结合复合物的主要组成部分,STAT5在TPO的作用下被酪氨酸磷酸化,此外,TPO诱导了STAT3的酪氨酸磷酸化和dna结合活性。结合最近对JAK2在TPO作用下激活的证明,本文提供的数据确定了一个可能在TPO诱导的基因调控中很重要的快速信号通路。
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.