Abstract
Signal Transduction The protein kinase GCN2 phosphorylates the translation initiation factor eIF2α and is an important component of signaling mechanisms that allow cells to coordinate rates of translation with the availability of amino acids. GCN2 is regulated by interaction with transfer RNAs, but Inglis et al. report that GCN2 can also directly interact with ribosomes in its role as a sensor of translation activity. Binding of a portion of the ribosome known as the P-stalk was enough to activate kinase activity of GCN2 toward eIF2α. This same region of the ribosome that interacts with GCN2 also interacts with elongation factors. This may provide a structural mechanism by which GCN2 could monitor translational stress. Proc. Natl. Acad. Sci. U.S.A. 116 , 4946 (2019).
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