G protein-coupled receptor APJ and its ligand apelin act downstream of Cripto to specify embryonic stem cells toward the cardiac lineage through extracellular signal-regulated kinase/p70S6 kinase signaling pathway
| Autor: | Giovanna L. Liguori, Peter Carmeliet, Monica Autiero, Ombretta Guardiola, Anna Maria Liguoro, Salvatore Iaconis, Gabriella Minchiotti, Cristina D'Aniello, Enza Lonardo |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: | |
| Zdroj: | Circulation research 105 (2009): 231–238. doi:10.1161/CIRCRESAHA.109.201186 info:cnr-pdr/source/autori:D'Aniello C.; Lonardo E..; Iaconis S; Guardiola O.; Liguoro A.M.; Liguori G.L.; Autiero M.; Carmeliet P.; Minchiotti G./titolo:G protein-coupled receptor APJ and its ligand apelin act downstream of Cripto to specify embryonic stem cells toward the cardiac lineage through extracellular signal-regulated kinase%2Fp70S6 kinase signaling pathway/doi:10.1161%2FCIRCRESAHA.109.201186/rivista:Circulation research/anno:2009/pagina_da:231/pagina_a:238/intervallo_pagine:231–238/volume:105 |
| DOI: | 10.1161/CIRCRESAHA.109.201186 |
| Popis: | Rationale: Pluripotent stem cells represent a powerful model system to study the early steps of cardiac specification for which the molecular control is largely unknown. The EGF-CFC (epidermal growth factor-Cripto/FRL-1/Cryptic) Cripto protein is essential for cardiac myogenesis in embryonic stem cells (ESCs). Objective: Here, we study the role of apelin and its G protein-coupled receptor, APJ, as downstream targets of Cripto both in vivo and in ESC differentiation. Methods and Results: Gain-of-function experiments show that APJ suppresses neuronal differentiation and restores the cardiac program in Cripto −/− ESCs. Loss-of-function experiments point for a central role for APJ/apelin in the gene regulatory cascade promoting cardiac specification and differentiation in ESCs. Remarkably, we show for the first time that apelin promotes mammalian cardiomyogenesis via activation of mitogen-activated protein kinase/p70S6 through coupling to a Go/Gi protein. Conclusions: Together our data provide evidence for a previously unrecognized function of APJ/apelin in the Cripto signaling pathway governing mesoderm patterning and cardiac specification in mammals. |
| Databáze: | OpenAIRE |
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