Coordinated cell motility is regulated by a combination of LKB1 farnesylation and kinase activityReport as inadecuate




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Journal Title:

Scientific Reports

Volume:

Volume 7

Publisher:

Nature Publishing Group: Open Access Journals - Option C | 2017-01-19

Type of Work:

Article | Final Publisher PDF

Abstract: Cell motility requires the precise coordination of cell polarization, lamellipodia formation, adhesion, and force generation. LKB1 is a multi-functional serine-threonine kinase that associates with actin at the cellular leading edge of motile cells and suppresses FAK. We sought to understand how LKB1 coordinates these multiple events by systematically dissecting LKB1 protein domain function in combination with live cell imaging and computational approaches. We show that LKB1-Actin colocalization is dependent upon LKB1 farnesylation leading to RhoA-ROCK-mediated stress fiber formation, but membrane dynamics is reliant on LKB1 kinase activity. We propose that LKB1 kinase activity controls membrane dynamics through FAK since loss of LKB1 kinase activity results in morphologically defective nascent adhesion sites. In contrast, defective farnesylation mislocalizes nascent adhesion sites, suggesting that LKB1 farnesylation serves as a targeting mechanism for properly localizing adhesion sites during cell motility. Together, we propose a model where coordination of LKB1 farnesylation and kinase activity serve as a multi-step mechanism to coordinate cell motility during migration.

Subjects: Health Sciences, Oncology - Biology, Bioinformatics - Biology, Biostatistics - Research Funding: This work was supported by grants R01CA142858 A.I.M., R01CA201340 A.I.M., 1R01CA194027 AIM, U24CA180924 J. S, U24CA194362 LADC and K22LM011576 LADC.

SW is supported by the National Institutes of Health under Ruth L. Kirschstein National Research Service Award 1F31CA200383-01 and was previously supported by a National Science Foundation Graduate Research Fellowship under Grant No. DGE-0940903.

SW is partially supported by the Laney Graduate School.

Research reported in this publication was supported in part by the Winship Cancer Institute, Emory Integrated Cellular Imaging Core, and Winship Biostatistics and Bioinformatics cores and NIH-NCI under award number P30CA138292.

mRuby-Paxillin-22 was a gift from Michael Davadison Addgene plasmid # 55877.

Keywords: Science and Technology - Multidisciplinary Sciences - Science and Technology - Other Topics - DEPENDENT PROTEIN-KINASE - FOCAL ADHESION KINASE - TUMOR-SUPPRESSOR - CANCER PROGRESSION - ACTIN DYNAMICS - SAD KINASES - LUNG - PROTRUSION - POLARIZATION - POLARITY -



Author: S. Wilkinson, Y. Hou, J. T. Zoine, J. Saltz, C. Zhang, Z. Chen, L. A. D. Cooper, Adam Marcus,

Source: https://open.library.emory.edu/



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