Bacon C M, Tortolani P J, Shimosaka A, Rees R C, Longo D L, O'Shea J J
Lymphocyte Cell Biology Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
FEBS Lett. 1995 Aug 14;370(1-2):63-8. doi: 10.1016/0014-5793(95)00796-c.
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.
巨核细胞的生长和分化受血小板生成素（TPO）调控，TPO是一种最近得以鉴定的细胞因子，它通过造血因子受体超家族成员c-Mpl发挥作用。由于许多结合造血因子受体的细胞因子可激活转录因子STAT家族，我们研究了STAT蛋白是否被TPO激活。TPO诱导形成一种识别已知STAT结合序列的DNA结合复合物。STAT5是该DNA结合复合物的主要成分，并且STAT5会响应TPO发生酪氨酸磷酸化。此外，TPO诱导STAT3的酪氨酸磷酸化和DNA结合活性。连同最近关于JAK2响应TPO而激活的证明，此处提供的数据定义了一条可能在TPO诱导的基因调控中起重要作用的快速信号通路。
