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.

Integration of TGF-beta and Ras/MAPK signaling through p53 phosphorylation

CORDENONSI, MICHELANGELO;MONTAGNER, MARCO;ADORNO, MADDALENA;ZACCHIGNA, LUCA;MARTELLO, GRAZIANO;MAMIDI, ANANT;SOLIGO, SANDRA MARIA;DUPONT, SIRIO;PICCOLO, STEFANO
2007

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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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/2443563
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