Cross-talk between the Smad1 and Ras/MEK signaling pathways for TCFβ

Jianbo Yue, Randall S. Frey, Kathleen Mulder

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

Our previous data demonstrated that Ras activation was necessary and sufficient for transforming growth factor-β (TGFβ)-mediated Erk1 activation, and was required for TGFβ up-regulation of the Cdk inhibitors (CKI's) p27(kip1) and p21(Cip1). Here we examined the role of Ras in TGFβ-mediated effects on a rat homolog of Smad1 (termed RSmad1). We demonstrate that both TGFβ and bone morphogenetic protein (BMP) can induce endogenous Smad1 phosphorylation in intestinal epithelial cells (IECs). The combination of transient expression of RSmad1 and TGFβ treatment had an additive effect on induction of the TGFβ-responsive reporter 3TP-lux. Either inactivation of Ras by stable, inducible expression of a dominant-negative mutant of Ras (RasN17) or addition of MAP and ERK kinase (MEK) inhibitor PD98059 to cells significantly decreased the ability of both TGFβ and BMP to induce phosphorylation of endogenous Smad1 in IECs. Moreover, either inactivation of Res or addition of PD98059 to IEC 4-1 cells inhibited the ability of RSmad1 to regulate 3TP luciferase activity in both the presence and absence of TGFβ. Collectively, our data indicate that TGFβ can regulate RSmad1 function in epithelial cells, and that the Ras/MEK pathway is partially required for TGFβ-mediated regulation of RSmad1.

Original languageEnglish (US)
Pages (from-to)2033-2037
Number of pages5
JournalOncogene
Volume18
Issue number11
DOIs
StatePublished - Mar 18 1999

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MAP Kinase Signaling System
Mitogen-Activated Protein Kinase Kinases
Transforming Growth Factors
Epithelial Cells
Bone Morphogenetic Proteins
Phosphorylation
Luciferases
Up-Regulation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Yue, Jianbo ; Frey, Randall S. ; Mulder, Kathleen. / Cross-talk between the Smad1 and Ras/MEK signaling pathways for TCFβ. In: Oncogene. 1999 ; Vol. 18, No. 11. pp. 2033-2037.
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Cross-talk between the Smad1 and Ras/MEK signaling pathways for TCFβ. / Yue, Jianbo; Frey, Randall S.; Mulder, Kathleen.

In: Oncogene, Vol. 18, No. 11, 18.03.1999, p. 2033-2037.

Research output: Contribution to journalArticle

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