RhoA and ROCK promote migration by limiting membrane protrusions - PubMed (original) (raw)

. 2003 Apr 11;278(15):13578-84.

doi: 10.1074/jbc.M211584200. Epub 2003 Feb 6.

Affiliations

• PMID: 12574166
• DOI: 10.1074/jbc.M211584200

Free article

RhoA and ROCK promote migration by limiting membrane protrusions

Rebecca A Worthylake et al. J Biol Chem. 2003.

Free article

Abstract

Previously, we and others have shown that RhoA and ROCK signaling are required for negatively regulating integrin-mediated adhesion and for tail retraction of migrating leukocytes. This study continues our investigation into the molecular mechanisms underlying RhoA/ROCK-regulated integrin adhesion. We show that inhibition of ROCK up-regulates integrin-mediated adhesion, which is accompanied by both increased phosphotyrosine signaling through Pyk-2 and paxillin and inappropriate membrane protrusions. We provide evidence that inhibition of ROCK induces integrin adhesion by promoting remodeling of the actin cytoskeleton. Furthermore, we find that ROCK regulates membrane activity through a pathway involving cofilin. Inhibition of RhoA signaling allows the formation of multiple competing lamellipodia that disrupt productive migration of monocytes. Together, our results show that RhoA/ROCK signaling promotes migration by restricting integrin activity and membrane protrusions to the leading edge.

PubMed Disclaimer

Similar articles

• Small guanosine triphospatase RhoA and Rho-associated kinase as regulators of trophoblast migration.
  Shiokawa S, Iwashita M, Akimoto Y, Nagamatsu S, Sakai K, Hanashi H, Kabir-Salmani M, Nakamura Y, Uehata M, Yoshimura Y. Shiokawa S, et al. J Clin Endocrinol Metab. 2002 Dec;87(12):5808-16. doi: 10.1210/jc.2002-020376. J Clin Endocrinol Metab. 2002. PMID: 12466390
• Organized migration of epithelial cells requires control of adhesion and protrusion through Rho kinase effectors.
  Hopkins AM, Pineda AA, Winfree LM, Brown GT, Laukoetter MG, Nusrat A. Hopkins AM, et al. Am J Physiol Gastrointest Liver Physiol. 2007 Mar;292(3):G806-17. doi: 10.1152/ajpgi.00333.2006. Epub 2006 Nov 30. Am J Physiol Gastrointest Liver Physiol. 2007. PMID: 17138966
• RhoA is required for monocyte tail retraction during transendothelial migration.
  Worthylake RA, Lemoine S, Watson JM, Burridge K. Worthylake RA, et al. J Cell Biol. 2001 Jul 9;154(1):147-60. doi: 10.1083/jcb.200103048. J Cell Biol. 2001. PMID: 11448997 Free PMC article.
• Small guanine nucleotide-binding protein Rho and myocardial function.
  Ren J, Fang CX. Ren J, et al. Acta Pharmacol Sin. 2005 Mar;26(3):279-85. doi: 10.1111/j.1745-7254.2005.00059.x. Acta Pharmacol Sin. 2005. PMID: 15715922 Review.
• [Rho-mediated signal transduction and its physiological roles].
  Ishizaki T. Ishizaki T. Nihon Yakurigaku Zasshi. 2003 Mar;121(3):153-62. doi: 10.1254/fpj.121.153. Nihon Yakurigaku Zasshi. 2003. PMID: 12673949 Review. Japanese.

Cited by

• Regulation of local expression of cell adhesion and motility-related mRNAs in breast cancer cells by IMP1/ZBP1.
  Gu W, Katz Z, Wu B, Park HY, Li D, Lin S, Wells AL, Singer RH. Gu W, et al. J Cell Sci. 2012 Jan 1;125(Pt 1):81-91. doi: 10.1242/jcs.086132. Epub 2012 Jan 20. J Cell Sci. 2012. PMID: 22266909 Free PMC article.
• Cooperative anti-invasive effect of Cdc42/Rac1 activation and ROCK inhibition in SW620 colorectal cancer cells with elevated blebbing activity.
  de Toledo M, Anguille C, Roger L, Roux P, Gadea G. de Toledo M, et al. PLoS One. 2012;7(11):e48344. doi: 10.1371/journal.pone.0048344. Epub 2012 Nov 7. PLoS One. 2012. PMID: 23144867 Free PMC article.
• ROCK1 and 2 differentially regulate actomyosin organization to drive cell and synaptic polarity.
  Newell-Litwa KA, Badoual M, Asmussen H, Patel H, Whitmore L, Horwitz AR. Newell-Litwa KA, et al. J Cell Biol. 2015 Jul 20;210(2):225-42. doi: 10.1083/jcb.201504046. Epub 2015 Jul 13. J Cell Biol. 2015. PMID: 26169356 Free PMC article.
• Cdc42 regulates neutrophil migration via crosstalk between WASp, CD11b, and microtubules.
  Kumar S, Xu J, Perkins C, Guo F, Snapper S, Finkelman FD, Zheng Y, Filippi MD. Kumar S, et al. Blood. 2012 Oct 25;120(17):3563-74. doi: 10.1182/blood-2012-04-426981. Epub 2012 Aug 29. Blood. 2012. PMID: 22932798 Free PMC article.
• Localized Ras signaling at the leading edge regulates PI3K, cell polarity, and directional cell movement.
  Sasaki AT, Chun C, Takeda K, Firtel RA. Sasaki AT, et al. J Cell Biol. 2004 Nov 8;167(3):505-18. doi: 10.1083/jcb.200406177. J Cell Biol. 2004. PMID: 15534002 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • The Lens - Patent Citations Database

• Miscellaneous

  • NCI CPTAC Assay Portal