Scrib regulates PAK activity during the cell migration process

Human Molecular Genetics
Sébastien NolaMarie-Josée Santoni

Abstract

Genetic studies have highlighted the key role of Scrib in the development of Metazoans. Deficiency in Scrib impairs many aspects of cell polarity and cell movement although the mechanisms involved remain unclear. In mammals, Scrib belongs to a protein complex containing betaPIX, an exchange factor for Rac/Cdc42, and GIT1, a GTPase activating protein for ARF6 implicated in receptor recycling and exocytosis. Here we show that the Scrib complex associates with PAK, a serine-threonine kinase family crucial for cell migration. PAK colocalizes with members of the Scrib complex at the leading edge of heregulin-treated T47D breast cancer cells. We demonstrate that the Scrib complex is required for epithelial cells and primary mouse embryonic fibroblasts to efficiently respond to chemoattractant cues. In Scrib-deficient cells, the pool of cortical PAK is decreased, thereby precluding its proper activation by Rac. Loss of Scrib also impairs the polarized distribution of active Rac at the leading edge and compromises the regulated activation of the GTPase in T47D cells and mouse embryonic fibroblasts. These data underscore the role of Scrib in cell migration and show the strong impact of Scrib in the function of PAK and Rac, two key molec...Continue Reading

References

Nov 25, 1998·Proceedings of the National Academy of Sciences of the United States of America·R T PremontR J Lefkowitz
Aug 12, 1999·Biochemical and Biophysical Research Communications·W LiuR A Roth
Nov 1, 2000·Cell·A Toker, A C Newton
Jan 3, 2001·The Journal of Cell Biology·M A SellsJ Chernoff
Jul 7, 2001·The Journal of Biological Chemistry·H SaitoJ P Borg
Nov 17, 2001·The Journal of Biological Chemistry·Fanny Jaulin-BastardJean-Paul Borg
Dec 26, 2001·Current Opinion in Structural Biology·B Kobe, A V Kajava
Sep 28, 2002·Trends in Genetics : TIG·Marie-Josée SantoniJean-Paul Borg
Dec 25, 2002·Human Molecular Genetics·Jennifer N MurdochAndrew J Copp
Apr 5, 2003·Annual Review of Biochemistry·Gary M Bokoch
Apr 24, 2003·Science's STKE : Signal Transduction Knowledge Environment·Claire NourryJean-Paul Borg
May 2, 2003·Nature·Mireille MontcouquiolMatthew W Kelley
Sep 26, 2003·Science of Aging Knowledge Environment : SAGE KE·Susheng Gan
Dec 19, 2003·Oncogene·Lukas E DowPatrick O Humbert
Apr 15, 2004·Molecular and Cellular Biology·Tsui-Han LooEd Manser
May 25, 2004·Nature Cell Biology·Romina MaroneAli Badache
Jun 9, 2004·Current Biology : CB·Stéphane AudebertJean-Paul Borg
Oct 16, 2004·Molecular Biology of the Cell·Susan LeeRichard A Firtel
Dec 22, 2004·The Journal of Cell Biology·Jennifer ZeitlerDavid Bilder
Mar 19, 2005·The EMBO Journal·Olivier LahunaMicheline Misrahi
Apr 5, 2005·Oncogene·Christel NavarroJean-Paul Borg
Jun 25, 2005·FEBS Letters·Jean-Yves MétaisJean-Paul Borg
Sep 1, 2005·The Journal of Cell Biology·Roumen PankovKenneth M Yamada
Oct 26, 2005·Molecular Cell·Zhuo-Shen ZhaoEd Manser
Nov 23, 2005·The Journal of Biological Chemistry·Penggao DaiLin Mei
Apr 7, 2006·Molecular Biology of the Cell·Konstadinos MoissogluMartin A Schwartz
Apr 7, 2006·Journal of Cell Science·Ryan J Hoefen, Bradford C Berk
Jun 23, 2006·Journal of Cellular Biochemistry·Laura M KallayLelita T Braiterman

❮ Previous
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Citations

Jan 24, 2009·Cancer Metastasis Reviews·Bettina DummlerJeffrey Field
Jan 17, 2008·Médecine sciences : M/S·Naël Osmani, Sandrine Etienne-Manneville
Jun 1, 2013·Molecular & Cellular Proteomics : MCP·Edwige BelottiJean-Paul Borg
Apr 24, 2009·Molecular Biology of the Cell·Dominic C Y PhuaWalter Hunziker
Jul 24, 2013·Annual Review of Cell and Developmental Biology·Sandrine Etienne-Manneville
Jan 14, 2011·American Journal of Physiology. Renal Physiology·Jay Pieczynski, Ben Margolis
May 25, 2012·Journal of Cell Science·Dennis J EastburnKeith E Mostov
Mar 27, 2009·Experimental & Molecular Medicine·Eun Young ShinEung Gook Kim
Aug 3, 2013·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Thaer KhouryJianmin Wang
Jan 5, 2016·Nature Reviews. Molecular Cell Biology·Roberto Mayor, Sandrine Etienne-Manneville
Jul 24, 2014·Small GTPases·Mirjam M Zegers, Peter Friedl
May 4, 2011·Birth Defects Research. Part A, Clinical and Molecular Teratology·Deborah J Henderson, Bill Chaudhry
Apr 7, 2012·Biochimica Et Biophysica Acta·Laurent PangonMaija R J Kohonen-Corish
Aug 27, 2013·European Journal of Cell Biology·Michael WigeriusMagnus Johansson
Aug 30, 2012·Essays in Biochemistry·Imogen ElsumHelena E Richardson
Sep 23, 2014·Experimental Cell Research·Michael Sebbagh, Jean-Paul Borg
Nov 20, 2012·Cellular Logistics·Diana Zi Ye, Jeffrey Field
Nov 20, 2012·Cellular Logistics·Zhuo-Shen Zhao, Ed Manser
Apr 7, 2010·Molecular and Cellular Neurosciences·Michael WigeriusMagnus Johansson
Aug 21, 2014·Cardiovascular Research·Veronika BoczonadiDeborah J Henderson
May 10, 2011·The American Journal of Pathology·Valentina VairaSilvano Bosari
Jun 7, 2016·Neuron·Isaac Cervantes-SandovalRonald L Davis
Dec 23, 2016·The Journal of Cell Biology·Tianliang SunThomas Worzfeld
Dec 14, 2017·The Journal of Cell Biology·Campbell D Lawson, Anne J Ridley
May 21, 2015·Cancer Informatics·Wan-Hsin LinPanos Z Anastasiadis
Aug 10, 2016·Journal of Cell Science·Janina HendrickMonilola A Olayioye
May 15, 2016·Journal of Cell Science·Leena BakerSenthil K Muthuswamy
Jan 31, 2013·Circulation Research·U Ruth MichaelisRalf P Brandes
Oct 16, 2015·PloS One·Christopher BoehlkeE Wolfgang Kuehn
Sep 12, 2015·Endocrine Reviews·Dolores D Mruk, C Yan Cheng
May 31, 2019·The Journal of Cell Biology·Jongho ChoiSergey M Troyanovsky

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