The Lipid Kinase PI5P4Kβ Is an Intracellular GTP Sensor for Metabolism and Tumorigenesis

Molecular Cell
Kazutaka SumitaAtsuo T Sasaki

Abstract

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 PI5P4Kβ, a phosphoinositide kinase that regulates PI(5)P levels, detects GTP concentration and converts them into lipid second messenger signaling. Biochemical analyses show that PI5P4Kβ 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 PI5P4Kβ is critical for metabolic adaptation and tumorigenesis. These results demonstrate that PI5P4Kβ is the missing GTP sensor and that GTP concentration functions as a metabolic cue via PI5P4Kβ. The critical role of the GTP-sensing activity of PI5P4Kβ in cancer signifies this lipid kinase as a cancer therapeutic target.

References

Nov 1, 1968·Archives of Biochemistry and Biophysics·R ErtelH Weissbach
Nov 9, 1994·Molecular and Cellular Biochemistry·T W Traut
Jan 1, 1997·Annual Review of Biochemistry·R Green, H F Noller
May 2, 2001·Genes & Development·M Ratnayake-LecamwasamA L Sonenshein
Nov 3, 2001·Science·P B DennisG Thomas
May 4, 2004·Nature Reviews. Molecular Cell Biology·Christopher J Schofield, Peter J Ratcliffe
Feb 17, 2006·Nature Reviews. Molecular Cell Biology·Boris N Kholodenko
Sep 18, 2008·International Journal of Obesity : Journal of the International Association for the Study of Obesity·D G Hardie
Mar 10, 2009·Genes & Development·Russell G Jones, Craig B Thompson
Apr 3, 2009·Nature Reviews. Molecular Cell Biology·Xiaoju Max Ma, John Blenis
Jun 2, 2009·Chemical Reviews·Lizbeth Hedstrom
Jul 31, 2009·Journal of Biomolecular Screening·Douglas J DemianMaura E Charlton
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Apr 27, 2010·FEBS Letters·Geoffrey GuittardJacques A Nunès
Jun 18, 2011·Science·Jonathan S OakhillBruce E Kemp
Sep 6, 2011·Nature Cell Biology·Maria M Mihaylova, Reuben J Shaw
Sep 29, 2011·Advances in Biological Regulation·Jonathan H Clarke, Robin F Irvine
Apr 17, 2012·Cell·Mathieu Laplante, David M Sabatini
Sep 27, 2012·Cancer Discovery·Jason R Cantor, David M Sabatini
Jul 9, 2013·Biochimica Et Biophysica Acta·Paolo PaoliPaola Chiarugi
Jun 7, 2014·Nature Communications·Julien ViaudFrédérique Gaits-Iacovoni
Jan 13, 2015·Molecular Cell·Mariella VicinanzaDavid C Rubinsztein
Jan 16, 2015·Journal of Cell Science·Frédéric BoalHélène Tronchère

❮ Previous
Next ❯

Citations

May 3, 2016·Trends in Biochemical Sciences·Roberta FiumeNullin Divecha
Sep 5, 2017·Nature Methods·Anna Bianchi-SmiragliaMikhail A Nikiforov
Jun 11, 2020·Mass Spectrometry Reviews·Ming Huang, Yinsheng Wang
Aug 12, 2020·Current Genetics·Christelle Saint-MarcBertrand Daignan-Fornier
May 1, 2019·International Journal of Molecular Sciences·Alessandro PoliNullin Divecha
Jul 24, 2020·Journal of Biochemistry·Satoshi Kofuji, Atsuo T Sasaki
Nov 5, 2019·Trends in Pharmacological Sciences·Thanh Kha PhanMark D Hulett
Mar 8, 2021·Current Opinion in Cell Biology·Padinjat Raghu
Feb 24, 2018·Advances in Biological Regulation·Suyong ChoiRichard A Anderson
May 19, 2021·Proceedings of the National Academy of Sciences of the United States of America·Song ChenYa Ha
Mar 5, 2020·Cell Chemical Biology·Sindhu Carmen SivakumarenNathanael S Gray
Aug 12, 2021·The Journal of Pathology. Clinical Research·Sofie Olsson HauKarin Jirström
Nov 26, 2021·FEBS Letters·Gurpreet K AroraBrooke M Emerling

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Metabolism

In order for cancer cells to maintain rapid, uncontrolled cell proliferation, they must acquire a source of energy. Cancer cells acquire metabolic energy from their surrounding environment and utilize the host cell nutrients to do so. Here is the latest research on cancer metabolism.

© 2022 Meta ULC. All rights reserved