Mathematical modeling of K-Ras nanocluster formation on the plasma membrane.

Biophysical Journal
Tianhai TianJohn F Hancock

Abstract

K-Ras functions as a critical node in the mitogen-activated protein kinase (MAPK) pathway that regulates key cellular functions including proliferation, differentiation, and apoptosis. Following growth factor receptor activation K-Ras.GTP forms nanoclusters on the plasma membrane through interaction with the scaffold protein galectin-3. The generation of nanoclusters is essential for high fidelity signal transduction via the MAPK pathway. To explore the mechanisms underlying K-Ras.GTP nanocluster formation, we developed a mathematical model of K-Ras-galectin-3 interactions. We designed a computational method to calculate protein collision rates based on experimentally determined protein diffusion rates and diffusion mechanisms and used a genetic algorithm to search the values of key model parameters. The optimal estimated model parameters were validated using experimental data. The resulting model accurately replicates critical features of K-Ras nanoclustering, including a fixed ratio of clustered K-Ras.GTP to monomeric K-Ras.GTP that is independent of the concentration of K-Ras.GTP. The model reproduces experimental results showing that the cytosolic level of galectin-3 determines the magnitude of the K-Ras.GTP clustered fract...Continue Reading

References

Aug 1, 1975·Proceedings of the National Academy of Sciences of the United States of America·P G Saffman, M Delbrück
Sep 17, 1996·Proceedings of the National Academy of Sciences of the United States of America·C Y Huang, J E Ferrell
Jan 2, 2003·Nature Reviews. Cancer·Julian Downward
Jan 16, 2003·The Journal of Cell Biology·Ian A PriorJohn F Hancock
Dec 10, 2003·Oncogene·Adrienne D Cox, Channing J Der
Apr 21, 2004·Proceedings of the National Academy of Sciences of the United States of America·Nizar N BatadaDavid O Siegmund
May 5, 2004·Proceedings of the National Academy of Sciences of the United States of America·Hideji MurakoshiAkihiro Kusumi
Apr 5, 2005·Genome Research·Hiroyuki KurataRei Iwasaki
Jun 16, 2005·The Biochemical Journal·John F Hancock, Robert G Parton
Oct 15, 2005·Proceedings of the National Academy of Sciences of the United States of America·Sarah J PlowmanJohn F Hancock
Oct 26, 2005·Physical Review Letters·Matthew S TurnerNicholas D Socci
Nov 18, 2005·FEBS Letters·Rainer Breitling, Daniela Hoeller
Feb 16, 2006·Biochimica Et Biophysica Acta·Jerka DumicMirna Flögel
Apr 21, 2006·Nature Reviews. Molecular Cell Biology·John F Hancock
Aug 22, 2006·Biophysical Journal·Piet H M LommerseThomas Schmidt
Dec 26, 2006·Biophysical Journal·Dan V NicolauKevin Burrage
Jul 10, 2007·Nature Cell Biology·Tianhai TianJohn F Hancock
Aug 19, 2007·Briefings in Bioinformatics·Kevin BurrageDan V Nicolau
Oct 17, 2007·The Journal of Cell Biology·Patrick LajoieIvan R Nabi
May 7, 2008·Molecular and Cellular Biology·Sarah J PlowmanJohn F Hancock
Jul 16, 2008·Trends in Cell Biology·Angus S Harding, John F Hancock
Aug 15, 2008·Cancer Research·Ruby Shalom-FeuersteinYoel Kloog

❮ Previous
Next ❯

Citations

Jun 7, 2012·Annals of Biomedical Engineering·Krishnan RadhakrishnanBridget S Wilson
Oct 16, 2013·Nano Letters·Derfogail DelcassianIain E Dunlop
Apr 8, 2016·Cellular Logistics·Tanmay Sanjeev ChavanVadim Gaponenko
Jan 28, 2016·Chemical Reviews·Shaoyong LuJian Zhang
Aug 25, 2012·Trends in Cell Biology·Khuloud Jaqaman, Sergio Grinstein
Mar 2, 2016·Proceedings of the National Academy of Sciences of the United States of America·Darius Vasco KösterSatyajit Mayor
Mar 18, 2016·Current Opinion in Cell Biology·Darius V Köster, Satyajit Mayor
Sep 20, 2011·Seminars in Cell & Developmental Biology·Ian A Prior, John F Hancock
May 9, 2012·Current Biology : CB·Kwang-jin ChoJohn F Hancock
Mar 13, 2012·Biophysical Journal·Andrew MuglerPieter Rein ten Wolde
Sep 23, 2014·Biochimica Et Biophysica Acta·Yong Zhou, John F Hancock
Nov 18, 2010·Biophysical Journal·Pinkesh BhagatjiJohn R Silvius
Nov 13, 2015·PloS One·Craig J MageeanIan A Prior
Dec 25, 2013·Molecular and Cellular Biology·Yong ZhouJohn F Hancock
Dec 13, 2017·Cold Spring Harbor Perspectives in Medicine·Yong ZhouJohn F Hancock
Dec 19, 2018·The Journal of Biological Chemistry·Bindu LakshmanFrantz L Jean-Francois
Oct 12, 2013·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Alexander WerkmüllerRoland Winter
Dec 3, 2016·Biochemical Society Transactions·Ana HerreroWalter Kolch
Apr 19, 2019·Scientific Reports·Aleksandra A FilkovaAnastasia N Sveshnikova
May 22, 2019·Physical Review. E·Wei-Xiang ChewSatya N V Arjunan
Jul 6, 2021·Frontiers in Molecular Biosciences·Yong ZhouJohn F Hancock
Jul 2, 2021·Chemical Science·Till RudackCarsten Kötting

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

© 2021 Meta ULC. All rights reserved