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

EMBO J. 2007 Mar 21;26(6):1522-31. doi: 10.1038/sj.emboj.7601598. Epub 2007 Feb 22.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line, Tumor
  • DNA Primers
  • Electrophoretic Mobility Shift Assay
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism
  • GRB7 Adaptor Protein / metabolism*
  • Immunoprecipitation
  • Mice
  • Nerve Growth Factors / metabolism*
  • Netrin-1
  • Phosphorylation
  • Protein Biosynthesis / physiology*
  • Receptors, Opioid, kappa / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / physiology*
  • Tumor Suppressor Proteins / metabolism*
  • Two-Hybrid System Techniques

Substances

  • DNA Primers
  • Nerve Growth Factors
  • Ntn1 protein, mouse
  • Receptors, Opioid, kappa
  • Tumor Suppressor Proteins
  • GRB7 Adaptor Protein
  • Netrin-1
  • Focal Adhesion Protein-Tyrosine Kinases