Smad2 transduces common signals from receptor serine–threonine and tyrosine kinases

  1. Mark P. de Caestecker1,
  2. W. Tony Parks1,
  3. Chistopher J. Frank1,
  4. Paola Castagnino2,
  5. Donald P. Bottaro2,
  6. Anita B. Roberts1, and
  7. Robert J. Lechleider1,3
  1. 1Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-5055 USA; 2Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892-4255 USA

Abstract

SMAD proteins mediate signals from receptor serine–threonine kinases (RSKs) of the TGF-β superfamily. We demonstrate here that HGF and EGF, which signal through RTKs, can also mediate SMAD-dependent reporter gene activation and induce rapid phosphorylation of endogenous SMAD proteins by kinase(s) downstream of MEK1. HGF induces phosphorylation and nuclear translocation of epitope-tagged Smad2 and a mutation that blocks TGF-β signaling also blocks HGF signal transduction. Smad2 may thus act as a common positive effector of TGF-β- and HGF-induced signals and serve to modulate cross talk between RTK and RSK signaling pathways.

Keywords

Footnotes

  • 3 Corresponding author.

  • E-MAIL lechleir{at}dce41.nci.nih.gov; FAX (301) 496-8395.

    • Received November 28, 1997.
    • Accepted April 13, 1998.
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