Hes binding to STAT3 mediates crosstalk between Notch and JAK-STAT signalling
Hes binding to STAT3 mediates crosstalk between Notch and JAK-STAT signalling
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DOI：
10.1038/ncb1138
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发表时间：
2004-06-01
影响因子：
21.3
通讯作者：
Gotoh, Y
中科院分区：
文献类型：
--
作者：
Kamakura, S;Oishi, K;Gotoh, Y
虽然Notch和JAK-STAT信号通路在生长和分化调节中发挥重叠的作用，但没有提出协调机制来解释它们的关系。在这里，我们表明，STAT 3激活的存在下，积极的Notch，以及Notch效应器Hes 1和Hes 5。Hes蛋白与JAK 2和STAT 3结合，促进JAK 2和STAT 3之间形成复合物，从而促进STAT 3的磷酸化和活化。此外，内源性Hes 1表达的抑制减少了生长因子对STAT 3磷酸化的诱导。STAT 3在发育中的中枢神经系统中通过Notch维持放射状胶质细胞和星形胶质细胞的分化似乎是必不可少的。这些结果表明，直接的蛋白质-蛋白质相互作用协调Notch-Hes和JAK-STAT途径之间的串扰。
Although the Notch and JAK-STAT signalling pathways fulfill overlapping roles in growth and differentiation regulation, no coordination mechanism has been proposed to explain their relationship. Here we show that STAT3 is activated in the presence of active Notch, as well as the Notch effectors Hes1 and Hes5. Hes proteins associate with JAK2 and STAT3, and facilitate complex formation between JAK2 and STAT3, thus promoting STAT3 phosphorylation and activation. Furthermore, suppression of endogenous Hes1 expression reduces growth factor induction of STAT3 phosphorylation. STAT3 seems to be essential for maintenance of radial glial cells and differentiation of astrocytes by Notch in the developing central nervous system. These results suggest that direct protein-protein interactions coordinate cross-talk between the Notch-Hes and JAK-STAT pathways.