The adaptor Grb7 links netrin-1 signaling to regulation of mRNA translation.
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.
Tsai
Nien-Pei
NP
Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Bi
Jing
J
Wei
Li-Na
LN
D000818:Animals; D045744:Cell Line, Tumor; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D051382:GRB7 Adaptor Protein / Q000378:metabolism*; D047468:Immunoprecipitation; D051379:Mice; D009414:Nerve Growth Factors / Q000378:metabolism*; D000075388:Netrin-1; D010766:Phosphorylation; D014176:Protein Biosynthesis / Q000502:physiology*; D017473:Receptors, Opioid, kappa / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D017931:DNA Primers; D009414:Nerve Growth Factors; C000617353:Ntn1 protein, mouse; D017473:Receptors, Opioid, kappa; D025521:Tumor Suppressor Proteins; D051382:GRB7 Adaptor Protein; D000075388:Netrin-1; D051416:Focal Adhesion Protein-Tyrosine Kinases