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.