Hes binding to STAT3 mediates crosstalk between Notch and JAK-STAT signalling

Sachiko Kamakura, Koji Oishi, Takeshi Yoshimatsu, Masato Nakafuku, Norihisa Masuyama, Yukiko Gotoh

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303 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)547-554
Number of pages8
JournalNature Cell Biology
Volume6
Issue number6
DOIs
Publication statusPublished - Jun 1 2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cell Biology

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    Kamakura, S., Oishi, K., Yoshimatsu, T., Nakafuku, M., Masuyama, N., & Gotoh, Y. (2004). Hes binding to STAT3 mediates crosstalk between Notch and JAK-STAT signalling. Nature Cell Biology, 6(6), 547-554. https://doi.org/10.1038/ncb1138