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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Substitution
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Animals
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Casein Kinase 1 epsilon / metabolism
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Casein Kinase Idelta / metabolism
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Cell Line, Tumor
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Cell Proliferation*
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Embryo, Nonmammalian / metabolism*
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Embryonic Development
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Embryonic Induction
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Fibroblast Growth Factors / metabolism
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Gene Expression Regulation, Developmental
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Humans
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Mesoderm / metabolism
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Mitogen-Activated Protein Kinases / metabolism*
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Phosphorylation
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Receptor Protein-Tyrosine Kinases / metabolism
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Signal Transduction*
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Smad Proteins / metabolism
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Transforming Growth Factor beta / metabolism*
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Tumor Suppressor Protein p53 / metabolism*
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Xenopus
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ras Proteins / metabolism*
Substances
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Smad Proteins
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Transforming Growth Factor beta
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Tumor Suppressor Protein p53
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Fibroblast Growth Factors
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Receptor Protein-Tyrosine Kinases
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Casein Kinase 1 epsilon
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Casein Kinase Idelta
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Mitogen-Activated Protein Kinases
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ras Proteins