The adaptor Grb7 links netrin-1 signaling to regulation of mRNA translation

Nien Pei Tsai, Jing Bi, Li-Na Wei

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

We previously reported a novel biological activity of Netrin-1 in translational stimulation of kappa opioid receptor (KOR). We now identify Grb7 as a new RNA-binding protein that serves as the molecular adaptor for transmitting Netrin-1 signals, through focal adhesion kinase (FAK), to the translation machinery. Grb7 binds specifically to the first stem loop of kor mRNA 5′-UTR through a new RNA-binding domain located in its amino terminus. Upon binding to its capped, target mRNA, Grb7 blocks the recruitment of eIF4E, rendering mRNA untranslatable. The RNA-binding and translation-repressive activity is reduced by FAK-mediated hyperphosphorylation on two tyrosine residues of its carboxyl terminus. This study reports an adaptor protein Grb7 that transmits the stimulating signals of Netrin-1 to the translational machinery to rapidly regulate mRNA translation.

Original languageEnglish (US)
Pages (from-to)1522-1531
Number of pages10
JournalEMBO Journal
Volume26
Issue number6
DOIs
StatePublished - Mar 21 2007

Keywords

  • Grb7
  • Netrin-1
  • RNA-binding protein
  • Translation

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