Letter abstract


Nature Cell Biology 6, 547 - 554 (2004)
Published online: 23 May 2004 | doi:10.1038/ncb1138

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

Sachiko Kamakura1, Koji Oishi1, Takeshi Yoshimatsu1, Masato Nakafuku2, Norihisa Masuyama1 & Yukiko Gotoh1,3,4

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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.

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  1. Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
  2. Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
  3. PRESTO and CREST Research Projects, Japan Science and Technology Corporation, Tokyo, Japan.
  4. National Institute for Physiological Sciences, 444-8585, Myodaiji, Okazaki, Japan.

Correspondence to: Yukiko Gotoh1,3,4 e-mail: ygotoh@iam.u-tokyo.ac.jp




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