Erbin suppresses the MAP kinase pathway

Yang Z. Huang, Mengwei Zang, Wencheng Xiong, Zhijun Luo, Lin Mei

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

We present evidence here that Erbin is a negative regulator of the Ras-Raf-Erk signaling pathway. Expression of Erbin decreases transcription of the AChR ε-subunit gene, an event that is mediated by Erk activation. Although it interacts with the ErbB2 C terminus through the PDZ domain, Erbin has no effect on ErbB2 tyrosine phosphorylation or binding to the adaptor proteins Shc and Grb2. In contrast, expression of Erbin greatly impairs activation of Erk, but not Akt, by ligands that activate receptor tyrosine kinases. Moreover, Erbin inhibits the Erk activation by active Ras, while it fails to do so in the presence of active Raf-1. Erbin associates with active Ras, but not inactive Ras nor Raf. Consistently, Erbin interferes with the interaction between Ras and Raf both in vivo and in vitro. Finally, overexpression of Erbin leads to inhibition of NGF-induced neuronal differentiation of PC12 cells, whereas downregulation of endogenous Erbin by specific siRNA exhibits an opposite effect. Collectively, our study has identified Erbin as a novel suppressor of the Ras signaling by disrupting the Ras-Raf interaction.

Original languageEnglish (US)
Pages (from-to)1108-1114
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number2
DOIs
StatePublished - Jan 10 2003

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Shc Signaling Adaptor Proteins
PDZ Domains
PC12 Cells
Receptor Protein-Tyrosine Kinases
Nerve Growth Factor
Small Interfering RNA
Tyrosine
Phosphotransferases
Down-Regulation
Chemical activation
Phosphorylation
Ligands
Genes
Transcription
In Vitro Techniques

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Huang, Y. Z., Zang, M., Xiong, W., Luo, Z., & Mei, L. (2003). Erbin suppresses the MAP kinase pathway. Journal of Biological Chemistry, 278(2), 1108-1114. https://doi.org/10.1074/jbc.M205413200

Erbin suppresses the MAP kinase pathway. / Huang, Yang Z.; Zang, Mengwei; Xiong, Wencheng; Luo, Zhijun; Mei, Lin.

In: Journal of Biological Chemistry, Vol. 278, No. 2, 10.01.2003, p. 1108-1114.

Research output: Contribution to journalArticle

Huang, YZ, Zang, M, Xiong, W, Luo, Z & Mei, L 2003, 'Erbin suppresses the MAP kinase pathway', Journal of Biological Chemistry, vol. 278, no. 2, pp. 1108-1114. https://doi.org/10.1074/jbc.M205413200
Huang YZ, Zang M, Xiong W, Luo Z, Mei L. Erbin suppresses the MAP kinase pathway. Journal of Biological Chemistry. 2003 Jan 10;278(2):1108-1114. https://doi.org/10.1074/jbc.M205413200
Huang, Yang Z. ; Zang, Mengwei ; Xiong, Wencheng ; Luo, Zhijun ; Mei, Lin. / Erbin suppresses the MAP kinase pathway. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 2. pp. 1108-1114.
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