Erbin suppresses the MAP kinase pathway

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

Research output: Contribution to journalArticlepeer-review

104 Scopus citations


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
Issue number2
StatePublished - Jan 10 2003
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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