Novel cross-talk between three cardiovascular regulators: thrombin cleavage fragment of Jagged1 induces fibroblast growth factor 1 expression and release
| Autor: | Deena Small, Robert Friesel, Joseph M. Verdi, Aleksandr Kirov, Raffaella Soldi, Igor Prudovsky, Doreen Kacer, Carla Mouta-Bellum, Maria F. Duarte, Lucy Liaw, Irene Graziani, Vihren Kolev, Thomas Maciag |
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| Rok vydání: | 2008 |
| Předmět: |
Transcription
Genetic Notch signaling pathway Biology Fibroblast growth factor Cell Line Mice Thrombin Thrombin receptor medicine Animals Humans Receptor PAR-1 Serrate-Jagged Proteins Molecular Biology Receptors Notch Multipotent Stem Cells Calcium-Binding Proteins Endothelial Cells Membrane Proteins Cardiovascular Agents Cell Biology Articles Receptors Fibroblast Growth Factor Peptide Fragments Cell biology Hairless Protein Structure Tertiary Molecular Weight Protein Transport Neural Crest Cardiovascular agent Jagged-1 Protein Fibroblast Growth Factor 1 Intercellular Signaling Peptides and Proteins Receptors Thrombin Signal transduction medicine.drug Signal Transduction |
| Zdroj: | Molecular biology of the cell. 19(11) |
| ISSN: | 1939-4586 |
| Popis: | Angiogenesis is controlled by several regulatory mechanisms, including the Notch and fibroblast growth factor (FGF) signaling pathways. FGF1, a prototype member of FGF family, lacks a signal peptide and is released through an endoplasmic reticulum–Golgi-independent mechanism. A soluble extracellular domain of the Notch ligand Jagged1 (sJ1) inhibits Notch signaling and induces FGF1 release. Thrombin, a key protease of the blood coagulation cascade and a potent inducer of angiogenesis, stimulates rapid FGF1 release through a mechanism dependent on the major thrombin receptor protease-activated receptor (PAR) 1. This study demonstrates that thrombin cleaves Jagged1 in its extracellular domain. The sJ1 form produced as a result of thrombin cleavage inhibits Notch-mediated CBF1/Suppressor of Hairless [(Su(H)]/Lag-1–dependent transcription and induces FGF1 expression and release. The overexpression of Jagged1 in PAR1 null cells results in a rapid thrombin-induced export of FGF1. These data demonstrate the existence of novel cross-talk between thrombin, FGF, and Notch signaling pathways, which play important roles in vascular formation and remodeling. |
| Databáze: | OpenAIRE |
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