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Abstract:
During development and tissue homeostasis, cells must integratedifferent signals. We investigated how cell behavior is controlledby the combined activity of transforming growth factor–ß(TGF-ß) 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-terminalphosphorylation, enabling the interaction of p53 with the TGF-ß–activatedSmads. This mechanism confines mesoderm specification in Xenopusembryos and promotes TGF-ß cytostasis in human cells.These data indicate a mechanism to allow extracellular cuesto specify the TGF-ß gene-expression program.
Department of Medical Biotechnologies, Section of Histology and Embryology, University of Padua, Padua, Italy.
* To whom correspondence should be addressed. E-mail: piccolo{at}civ.bio.unipd.it
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