Integration of TGF-beta and Ras/MAPK signaling through p53 phosphorylation |
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| Authors: | Cordenonsi Michelangelo Montagner Marco Adorno Maddalena Zacchigna Luca Martello Graziano Mamidi Anant Soligo Sandra Dupont Sirio Piccolo Stefano |
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| Institution: | Department of Medical Biotechnologies, Section of Histology and Embryology, University of Padua, Padua, Italy. |
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| Abstract: | During development and tissue homeostasis, cells must integrate different signals. We investigated how cell behavior is controlled by the combined activity of transforming growth factor-beta (TGF-beta) and receptor tyrosine kinase (RTK) signaling, whose integration mechanism is unknown. We find that RTK/Ras/MAPK (mitogen-activated protein kinase) activity induces p53 N-terminal phosphorylation, enabling the interaction of p53 with the TGF-beta-activated Smads. This mechanism confines mesoderm specification in Xenopus embryos and promotes TGF-beta cytostasis in human cells. These data indicate a mechanism to allow extracellular cues to specify the TGF-beta gene-expression program. |
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