Integration of TGF-ß and Ras/MAPK Signaling Through p53 Phosphorylation

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Science  09 Feb 2007:
Vol. 315, Issue 5813, pp. 840-843
DOI: 10.1126/science.1135961

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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–β (TGF-β) 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-β–activated Smads. This mechanism confines mesoderm specification in Xenopus embryos and promotes TGF-β cytostasis in human cells. These data indicate a mechanism to allow extracellular cues to specify the TGF-β gene-expression program.

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