3x01

Publication Abstract from PubMed

While cellular GTP concentration dramatically changes in response to an organism's cellular status, whether it serves as a metabolic cue for biological signaling remains elusive due to the lack of molecular identification of GTP sensors. Here we report that PI5P4Kbeta, a phosphoinositide kinase that regulates PI(5)P levels, detects GTP concentration and converts them into lipid second messenger signaling. Biochemical analyses show that PI5P4Kbeta preferentially utilizes GTP, rather than ATP, for PI(5)P phosphorylation, and its activity reflects changes in direct proportion to the physiological GTP concentration. Structural and biological analyses reveal that the GTP-sensing activity of PI5P4Kbeta is critical for metabolic adaptation and tumorigenesis. These results demonstrate that PI5P4Kbeta is the missing GTP sensor and that GTP concentration functions as a metabolic cue via PI5P4Kbeta. The critical role of the GTP-sensing activity of PI5P4Kbeta in cancer signifies this lipid kinase as a cancer therapeutic target.

The Lipid Kinase PI5P4Kbeta Is an Intracellular GTP Sensor for Metabolism and Tumorigenesis.,Sumita K, Lo YH, Takeuchi K, Senda M, Kofuji S, Ikeda Y, Terakawa J, Sasaki M, Yoshino H, Majd N, Zheng Y, Kahoud ER, Yokota T, Emerling BM, Asara JM, Ishida T, Locasale JW, Daikoku T, Anastasiou D, Senda T, Sasaki AT Mol Cell. 2016 Jan 21;61(2):187-98. doi: 10.1016/j.molcel.2015.12.011. Epub 2016 , Jan 7. PMID:26774281^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.