Integration of TGF-beta and Ras/MAPK signaling through p53 phosphorylation.
Cordenonsi, Michelangelo ; Montagner, Marco ; Adorno, Maddalena ; et al. ; - ASI Sponsor
Feb - 2007
ISSN : 1095-9203 ;
journal : Science (New York, N.Y.)
Issue : 5813
type: Article Journal
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.
keywords : Amino Acid Substitution,Animals,Casein Kinase Idelta,Casein Kinase Idelta: metabolism,Casein Kinase Iepsilon,Casein Kinase Iepsilon: metabolism,Cell Line,Cell Proliferation,Developmental,Embryo,Embryonic Development,Embryonic Induction,Fibroblast Growth Factors,Fibroblast Growth Factors: metabolism,Gene Expression Regulation,Humans,Mesoderm,Mesoderm: metabolism,Mitogen-Activated Protein Kinases,Mitogen-Activated Protein Kinases: metabolism,Nonmammalian,Nonmammalian: metabolism,Phosphorylation,Receptor Protein-Tyrosine Kinases,Receptor Protein-Tyrosine Kinases: metabolism,Signal Transduction,Smad Proteins,Smad Proteins: metabolism,Transforming Growth Factor beta,Transforming Growth Factor beta: metabolism,Tumor,Tumor Suppressor Protein p53,Tumor Suppressor Protein p53: metabolism,Xenopus,ras Proteins,ras Proteins: metabolism