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

نویسندگان

  • Michelangelo Cordenonsi
  • Marco Montagner
  • Maddalena Adorno
  • Luca Zacchigna
  • Graziano Martello
  • Anant Mamidi
  • Sandra Soligo
  • Sirio Dupont
  • Stefano Piccolo
چکیده

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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عنوان ژورنال:
  • Science

دوره 315 5813  شماره 

صفحات  -

تاریخ انتشار 2007