biostudies-literatureWilkinson SNCI NIH HHSNLM NIH HHS40929https://www.ebi.ac.uk/biostudies/studies/S-EPMC5244416biostudies-literatureUnknown7Cell 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 naScientific reportsCoordinated cell motility is regulated by a combination of LKB1 farnesylation and kinase activity.PMC5244416R01 CA201340R01 CA194027U24 CA180924F31 CA200383U24 CA194362P30 CA138292R01 LM009239R01 CA142858K22 LM011576Chen ZMarcus AIZoine JTCooper LAZhang CHou YSaltz JWilkinson SfalseCoordinated cell motility is regulated by a combination of LKB1 farnesylation and kinase activity.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 na2017-01-01T00:00:00Z2017 Jan2025-04-26T12:11:14.204Z2019-03-27T02:34:28ZS-EPMC52444162810231010.1038/srep40929