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Synergy and antagonism between Notch and BMP receptor signaling pathways in endothelial cells
Author(s) -
Itoh Fumiko,
Itoh Susumu,
Goumans MarieJosé,
Valdimarsdottir Gudrun,
Iso Tatsuya,
Dotto G Paolo,
Hamamori Yasuo,
Kedes Larry,
Kato Mitsuyasu,
Dijke Peter ten
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600065
Subject(s) - notch signaling pathway , biology , hes3 signaling axis , microbiology and biotechnology , signal transduction , smad , bone morphogenetic protein , downregulation and upregulation , effector , bmpr2 , receptor , genetics , gene
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‐Jκ/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.