Dual action of epidermal growth factor: Extracellular signal-stimulated nuclear-cytoplasmic export and coordinated translation of selected messenger RNA

Nien Pei Tsai, Yu-Lung Lin, Yao Chen Tsui, Li-Na Wei

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

We report the first example of a coordinated dual action of epidermal growth factor (EGF) in stimulating the nuclear-cytoplasmic export and translation of a select messenger RNA (mRNA). The effect of EGF is mediated by the RNA-binding protein Grb7 (growth factor receptor-bound protein 7), which serves as an adaptor for a specific mRNA-protein export complex and a translational regulator. Using the κ-opioid receptor (OR [KOR]) as a model, we demonstrate that EGF activates nuclear SHP-2 (Src homology region 2-containing tyrosine phosphatase), which dephosphorylates Grb7 in the nucleus. Hypophosphorylated Grb7 binds to the KOR mRNA and recruits the Hu antigen R-exportin-1 (CRM1) complex to form a nuclear-cytoplasmic export complex that exports KOR mRNA. EGF also activates focal adhesion kinase in the cytoplasm to rephosphorylate Grb7, releasing KOR mRNA for active translation. In summary, this study uncovers a coordinated, dual activity of EGF in facilitating nuclear export of a specific mRNA-protein complex as well as translational activation of the exported mRNA.

Original languageEnglish (US)
Pages (from-to)325-333
Number of pages9
JournalJournal of Cell Biology
Volume188
Issue number3
DOIs
StatePublished - Feb 8 2010

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