title: Stimulation of Id1 expression by bone morphogenetic protein is sufficient and necessary for bone morphogenetic protein-induced activation of endothelial cells.
abstract: BACKGROUND
  Bone morphogenetic proteins (BMPs) are multifunctional proteins that regulate the proliferation, differentiation, and migration of a large variety of cell types. Like other members of the transforming growth factor-beta family, BMPs elicit their cellular effects through activating specific combinations of type I and type II serine/threonine kinase receptors and their downstream effector proteins, which are termed Smads. In the present study, we investigated BMP receptor/Smad expression and signaling in endothelial cells (ECs) and examined the effects of BMP on EC behavior.
  
  
  RESULTS
  Immunohistochemical analysis of tissue sections of human colon and mouse heart and aorta showed that BMP receptors are expressed in ECs in vivo. Bovine aortic ECs and mouse embryonic ECs were found to express BMP receptors and their Smads. BMP receptor activation induced the phosphorylation of specific Smad proteins and promoted EC migration and tube formation. Id1 was identified as a BMP/Smad target in ECs. Ectopic expression of Id1 mimicked BMP-induced effects. Importantly, specific interference with Id1 expression blocked BMP-induced EC migration.
  
  
  CONCLUSIONS
  The BMP/Smad pathway can potently activate the endothelium. Id1 expression is strongly induced by BMP in ECs. Ectopic expression of Id1 induces EC migration and tube formation. Moreover, Id1 played a critical role in mediating BMP-induced EC migration.
authors.affiliation: Division of Cellular Biochemistry, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Valdimarsdottir
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Goumans
authors.forename: Alexander
authors.initials: A
authors.lastname: Rosendahl
authors.forename: Martijn
authors.initials: M
authors.lastname: Brugman
authors.forename: Susumu
authors.initials: S
authors.lastname: Itoh
authors.forename: Franck
authors.initials: F
authors.lastname: Lebrin
authors.forename: Paschalis
authors.initials: P
authors.lastname: Sideras
authors.forename: Peter
authors.initials: P
authors.lastname: ten Dijke
mesh_terms: D000818:Animals; D055418:Bone Morphogenetic Protein 6; D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002417:Cattle; D002465:Cell Movement; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism* / Q000502:physiology*; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1; D051379:Mice; D018919:Neovascularization, Physiologic; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000378:metabolism; D017978:Receptors, Growth Factor; D012097:Repressor Proteins; D015398:Signal Transduction; D051902:Smad5 Protein; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation
chemical_list: C525816:BMP6 protein, human; C525817:Bmp6 protein, mouse; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; C497453:ID1 protein, human; C497455:Idb1 protein, mouse; D051798:Inhibitor of Differentiation Protein 1; D010750:Phosphoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D012097:Repressor Proteins; C497797:SMAD5 protein, human; D051902:Smad5 Protein; C497798:Smad5 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D052004:Bone Morphogenetic Protein Receptors