Synergy and antagonism between Notch and BMP receptor signaling pathways in endothelial cells

Autor: G. Paolo Dotto, Gudrun Valdimarsdottir, Peter ten Dijke, Marie-José Goumans, Fumiko Itoh, Yasuo Hamamori, Susumu Itoh, Tatsuya Iso, Larry Kedes, Mitsuyasu Kato
Rok vydání: 2004
Předmět:
Inhibitor of Differentiation Protein 1
Cellular differentiation
Notch signaling pathway
Down-Regulation
Smad Proteins
SMAD
Biology
Bone morphogenetic protein
Article
General Biochemistry
Genetics and Molecular Biology
Mice
Cell Movement
Chlorocebus aethiops
Animals
Humans
Receptors
Growth Factor
Promoter Regions
Genetic
Molecular Biology
Receptors
Notch
General Immunology and Microbiology
General Neuroscience
Endothelial Cells
Membrane Proteins
Nuclear Proteins
Bone Morphogenetic Protein Receptors
Molecular biology
GC Rich Sequence
Up-Regulation
BMPR2
Cell biology
DNA-Binding Proteins
Repressor Proteins
Notch proteins
Hes3 signaling axis
Immunoglobulin J Recombination Signal Sequence-Binding Protein
COS Cells
Trans-Activators
Cyclin-dependent kinase 8
Signal Transduction
Transcription Factors
Zdroj: The EMBO Journal. 23:541-551
ISSN: 1460-2075
0261-4189
DOI: 10.1038/sj.emboj.7600065
Popis: Notch and bone morphogenetic protein signaling pathways are important for cellular differentiation, and both have been implicated in vascular development. In many cases the two pathways act similarly, but antagonistic effects have also been reported. The underlying mechanisms and whether this is caused by an interplay between Notch and BMP signaling is unknown. Here we report that expression of the Notch target gene, Herp2, is synergistically induced upon activation of Notch and BMP receptor signaling pathways in endothelial cells. The synergy is mediated via RBP-Jkappa/CBF-1 and GC-rich palindromic sites in the Herp2 promoter, as well as via interactions between the Notch intracellular domain and Smad that are stabilized by p/CAF. Activated Notch and its downstream effector Herp2 were found to inhibit endothelial cell (EC) migration. In contrast, BMP via upregulation of Id1 expression has been reported to promote EC migration. Interestingly, Herp2 was found to antagonize BMP receptor/Id1-induced migration by inhibiting Id1 expression. Our results support the notion that Herp2 functions as a critical switch downstream of Notch and BMP receptor signaling pathways in ECs.
Databáze: OpenAIRE
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