Activation of a GPCR leads to eIF4G phosphorylation at the 5 ' cap and to IRES-dependent translation

作者：Leon Kelly; Boulo Thomas; Musnier Astrid; Morales Julia; Gauthier Christophe; Dupuy Laurence; Heyne Steffen; Backofen Rolf; Poupon Anne; Cormier Patrick; Reiter Eric; Crepieux Pascale^*

来源：Journal of Molecular Endocrinology, 2014, 52(3): 373-382.

DOI：10.1530/JME-14-0009

• GPCR
• FSH
• mRNA translation
• eIF4G
• IRES
• HEK293 cells

The control of mRNA translation has been mainly explored in response to activated tyrosine kinase receptors. In contrast, mechanistic details on the translational machinery are far less available in the case of ligand-bound G protein-coupled receptors (GPCRs). In this study, using the FSH receptor (FSH-R) as a model receptor, we demonstrate that part of the translational regulations occurs by phosphorylation of the translation pre-initiation complex scaffold protein, eukaryotic initiation factor 4G (eIF4G), in HEK293 cells stably expressing the FSH-R. This phosphorylation event occurred when eIF4G was bound to the mRNA 50 cap, and probably involves mammalian target of rapamycin. This regulation might contribute to cap-dependent translation in response to FSH. The cap-binding protein eIF4E also had its phosphorylation level enhanced upon FSH stimulation. We also show that FSH-induced signaling not only led to cap-dependent translation but also to internal ribosome entry site (IRES)-dependent translation of some mRNA. These data add detailed information on the molecular bases underlying the regulation of selective mRNA translation by a GPCR, and a topological model recapitulating these mechanisms is proposed.

• 出版日期2014-6