Hes binding to STAT3 mediates crosstalk between Notch and JAK-STAT signalling.
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.
Kamakura
Sachiko
S
Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Oishi
Koji
K
Yoshimatsu
Takeshi
T
Nakafuku
Masato
M
Masuyama
Norihisa
N
Gotoh
Yukiko
Y
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins; D019556:COS Cells; D002454:Cell Differentiation / Q000502:physiology; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005333:Fetus; D018398:Homeodomain Proteins / Q000378:metabolism*; D053614:Janus Kinase 2; D051379:Mice; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D000072056:Transcription Factor HES-1; D014157:Transcription Factors
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D053614:Janus Kinase 2; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; D015534:Trans-Activators; D000072056:Transcription Factor HES-1; D014157:Transcription Factors; C489734:Hes1 protein, mouse; C489685:Hes5 protein, mouse; C497762:Notch1 protein, mouse; C494087:Stat3 protein, mouse; C077478:HES5 protein, human; C507924:JAK2 protein, human; C507926:Jak2 protein, mouse