Integration of TGF-β and Ras/MAPK Signaling Through p53 Phosphorylation
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-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.
- Publication:
-
Science
- Pub Date:
- February 2007
- DOI:
- 10.1126/science.1135961
- Bibcode:
- 2007Sci...315..840C
- Keywords:
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- Developmental Biology