RT Journal Article SR Electronic T1 A Year in Structural Signaling: mTOR—The PIKK of the Bunch? JF Science Signaling JO Sci. Signal. FD American Association for the Advancement of Science SP pe6 OP pe6 DO 10.1126/scisignal.2005174 VO 7 IS 315 A1 Smerdon, Stephen J. YR 2014 UL http://stke.sciencemag.org/content/7/315/pe6.abstract AB The phosphatidylinositol 3-kinase–like protein kinases (PIKKs) are large, atypical serine-threonine kinases that function in many important cellular signaling processes. Despite their prominence, and due to the complexity of their architecture and interactions, PIKKs have long managed to evade high-resolution crystallographic analysis. Recent, near–atomic-resolution structures of nucleotide- and inhibitor-bound complexes of a large carboxyl-terminal fragment of mammalian target of rapamycin (mTOR) are set to transform our understanding of the expansive signaling functions of these fascinating molecules and inform efforts to design therapeutic agents against a broad spectrum of human diseases ranging from diabetes to cancer.