Home LiteratureArticle Details
PMID: 19339277 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Reactive oxygen species regulate a slingshot-cofilin activation pathway.

Molecular biology of the cell ·Vol. 20 ·No. 11 ·2009-06-00 ·Pages 2650-60

Kim JS, Huang TY, Bokoch GM

Abstract

Cellular stimuli generate reactive oxygen species (ROS) via the local action of NADPH oxidases (Nox) to modulate cytoskeletal organization and cell migration through unknown mechanisms. Cofilin is a major regulator of cellular actin dynamics whose activity is controlled by phosphorylation/dephosphorylation at Ser3. Here we show that Slingshot-1L (SSH-1L), a selective cofilin regulatory phosphatase, is involved in H(2)O(2)-induced cofilin dephosphorylation and activation. SSH-1L is activated by its release from a regulatory complex with 14-3-3zeta protein through the redox-mediated oxidation of 14-3-3zeta by H(2)O(2). The ROS-dependent activation of the SSH-1L-cofilin pathway stimulates the SSH-1L-dependent formation of cofilin-actin rods in cofilin-GFP-expressing HeLa cells. Similarly, the formation of endogenous ROS stimulated by angiotensin II (AngII) also activates the SSH-1L-cofilin pathway via oxidation of 14-3-3zeta to increase AngII-induced membrane ruffling and cell motility. These results suggest that the formation of ROS by NADPH oxidases engages a SSH-1L-cofilin pathway to regulate cytoskeletal organization and cell migration.

MeSH Terms
14-3-3 Proteins/metabolism Angiotensin II/pharmacology Blotting, Western Cell Line, Tumor Cell Movement/drug effects Cofilin 1/genetics,metabolism Green Fluorescent Proteins/genetics,metabolism HeLa Cells Humans Hydrogen Peroxide/pharmacology Microscopy, Fluorescence NADPH Oxidase 1 NADPH Oxidases/genetics,metabolism Oxidants/pharmacology Oxidation-Reduction/drug effects Phosphoprotein Phosphatases/genetics,metabolism Phosphorylation/drug effects Protein Binding/drug effects RNA, Small Interfering/genetics Reactive Oxygen Species/metabolism Signal Transduction Transfection
Chemicals
14-3-3 Proteins Cofilin 1 Oxidants RNA, Small Interfering Reactive Oxygen Species Angiotensin II Green Fluorescent Proteins Hydrogen Peroxide NADPH Oxidase 1 NADPH Oxidases NOX1 protein, human Phosphoprotein Phosphatases SSH1 protein, human
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Kim Jun-Sub
Department of Immunology and Microbial Science and Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Huang Timothy Y
Bokoch Gary M
References (57)
57 references, click to expand
  1. Probing cellular protein targets of H2O2 with fluorescein-conjugated iodoacetamide and antibodies to fluorescein.
    FEBS Lett. 1998 Nov 27;440(1-2):111-5 PMID: 9862437
  2. Proteomic profiling and identification of cofilin responding to oxidative stress in vascular smooth muscle.
    Proteomics. 2006 Dec;6(24):6455-75 PMID: 17099934
  3. Vascular NAD(P)H oxidases: specific features, expression, and regulation.
    Am J Physiol Regul Integr Comp Physiol. 2003 Aug;285(2):R277-97 PMID: 12855411
  4. Regulation of Nox and Duox enzymatic activity and expression.
    Free Radic Biol Med. 2007 Aug 1;43(3):319-31 PMID: 17602947
  5. Chronophin mediates an ATP-sensing mechanism for cofilin dephosphorylation and neuronal cofilin-actin rod formation.
    Dev Cell. 2008 Nov;15(5):691-703 PMID: 19000834
  6. Cofilin undergoes rapid dephosphorylation in stimulated neutrophils and translocates to ruffled membranes enriched in products of the NADPH oxidase complex. Evidence for a novel cycle of phosphorylation and dephosphorylation.
    Histochem Cell Biol. 1997 Sep;108(3):221-33 PMID: 9342616
  7. Production of large amounts of hydrogen peroxide by human tumor cells.
    Cancer Res. 1991 Feb 1;51(3):794-8 PMID: 1846317
  8. NADPH oxidases and angiotensin II receptor signaling.
    Mol Cell Endocrinol. 2009 Apr 29;302(2):148-58 PMID: 19059306
  9. Interplay between components of a novel LIM kinase-slingshot phosphatase complex regulates cofilin.
    EMBO J. 2005 Feb 9;24(3):473-86 PMID: 15660133
  10. Chronophin, a novel HAD-type serine protein phosphatase, regulates cofilin-dependent actin dynamics.
    Nat Cell Biol. 2005 Jan;7(1):21-9 PMID: 15580268
  11. Nox1 is over-expressed in human colon cancers and correlates with activating mutations in K-Ras.
    Int J Cancer. 2008 Jul 1;123(1):100-7 PMID: 18398843
  12. Calcium signal-induced cofilin dephosphorylation is mediated by Slingshot via calcineurin.
    J Biol Chem. 2005 Apr 1;280(13):12683-9 PMID: 15671020
  13. Transforming growth factor-beta1 regulates macrophage migration via RhoA.
    Blood. 2006 Sep 15;108(6):1821-9 PMID: 16705092
  14. Mechanism of angiotensin II-induced superoxide production in cells reconstituted with angiotensin type 1 receptor and the components of NADPH oxidase.
    J Biol Chem. 2008 Jan 4;283(1):255-267 PMID: 17981802
  15. The structure and regulation of protein phosphatases.
    Adv Second Messenger Phosphoprotein Res. 1990;24:230-5 PMID: 2169802
  16. The slingshot family of phosphatases mediates Rac1 regulation of cofilin phosphorylation, laminin-332 organization, and motility behavior of keratinocytes.
    J Biol Chem. 2007 Nov 2;282(44):32520-8 PMID: 17848544
  17. ROS-generating mitochondrial DNA mutations can regulate tumor cell metastasis.
    Science. 2008 May 2;320(5876):661-4 PMID: 18388260
  18. Neurodegenerative stimuli induce persistent ADF/cofilin-actin rods that disrupt distal neurite function.
    Nat Cell Biol. 2000 Sep;2(9):628-36 PMID: 10980704
  19. Compartmentalization of redox signaling through NADPH oxidase-derived ROS.
    Antioxid Redox Signal. 2009 Jun;11(6):1289-99 PMID: 18999986
  20. Effect of reactive oxygen intermediates on the in vitro invasive capacity of tumor cells and liver metastasis in mice.
    Int J Cancer. 1993 Jul 30;54(6):983-6 PMID: 8392985
  21. Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system.
    Am J Physiol Cell Physiol. 2007 Jan;292(1):C82-97 PMID: 16870827
  22. Novel gp91(phox) homologues in vascular smooth muscle cells : nox1 mediates angiotensin II-induced superoxide formation and redox-sensitive signaling pathways.
    Circ Res. 2001 May 11;88(9):888-94 PMID: 11348997
  23. Mechanisms of vascular smooth muscle NADPH oxidase 1 (Nox1) contribution to injury-induced neointimal formation.
    Arterioscler Thromb Vasc Biol. 2009 Apr;29(4):480-7 PMID: 19150879
  24. Quantification and morphologic demonstration of reactive oxygen species produced by Walker 256 tumor cells in vitro and during metastasis in vivo.
    Lab Invest. 1994 Oct;71(4):480-9 PMID: 7967504
  25. Regulation of the actin cytoskeleton in cancer cell migration and invasion.
    Biochim Biophys Acta. 2007 May;1773(5):642-52 PMID: 16926057
  26. The signaling mechanism of ROS in tumor progression.
    Cancer Metastasis Rev. 2006 Dec;25(4):695-705 PMID: 17160708
  27. Redox changes of cultured endothelial cells and actin dynamics.
    Circ Res. 2000 Mar 17;86(5):549-57 PMID: 10720417
  28. Regulation of actin dynamics through phosphorylation of cofilin by LIM-kinase.
    Nature. 1998 Jun 25;393(6687):805-9 PMID: 9655397
  29. Vascular endothelial growth factor causes translocation of p47phox to membrane ruffles through WAVE1.
    J Biol Chem. 2003 Sep 19;278(38):36830-40 PMID: 12855698
  30. NADPH oxidases: not just for leukocytes anymore!
    Trends Biochem Sci. 2003 Sep;28(9):502-8 PMID: 13678962
  31. Regulation of actin filament network formation through ARP2/3 complex: activation by a diverse array of proteins.
    Annu Rev Biochem. 2001;70:649-76 PMID: 11395419
  32. Regulation of signal transduction through protein cysteine oxidation.
    Antioxid Redox Signal. 2006 Sep-Oct;8(9-10):1819-27 PMID: 16987034
  33. Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin reorganization.
    Nature. 1998 Jun 25;393(6687):809-12 PMID: 9655398
  34. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology.
    Physiol Rev. 2007 Jan;87(1):245-313 PMID: 17237347
  35. Cofilin phosphatases and regulation of actin dynamics.
    Curr Opin Cell Biol. 2006 Feb;18(1):26-31 PMID: 16337782
  36. Control of actin reorganization by Slingshot, a family of phosphatases that dephosphorylate ADF/cofilin.
    Cell. 2002 Jan 25;108(2):233-46 PMID: 11832213
  37. IQGAP1 regulates reactive oxygen species-dependent endothelial cell migration through interacting with Nox2.
    Arterioscler Thromb Vasc Biol. 2005 Nov;25(11):2295-300 PMID: 16179592
  38. Phosphoinositide-dependent kinase 1 and p21-activated protein kinase mediate reactive oxygen species-dependent regulation of platelet-derived growth factor-induced smooth muscle cell migration.
    Circ Res. 2004 May 14;94(9):1219-26 PMID: 15059930
  39. Spatial and temporal regulation of cofilin activity by LIM kinase and Slingshot is critical for directional cell migration.
    J Cell Biol. 2005 Oct 24;171(2):349-59 PMID: 16230460
  40. Redox redux: revisiting PTPs and the control of cell signaling.
    Cell. 2005 Jun 3;121(5):667-70 PMID: 15935753
  41. Arp2/3 complex and actin depolymerizing factor/cofilin in dendritic organization and treadmilling of actin filament array in lamellipodia.
    J Cell Biol. 1999 May 31;145(5):1009-26 PMID: 10352018
  42. Proteins of the ADF/cofilin family: essential regulators of actin dynamics.
    Annu Rev Cell Dev Biol. 1999;15:185-230 PMID: 10611961
  43. Regulation of Nox1 activity via protein kinase A-mediated phosphorylation of NoxA1 and 14-3-3 binding.
    J Biol Chem. 2007 Nov 30;282(48):34787-800 PMID: 17913709
  44. Oxidative damage of 14-3-3 zeta and gamma isoforms in Alzheimer's disease and cerebral amyloid angiopathy.
    Neuroscience. 2007 Jun 8;146(4):1640-51 PMID: 17445990
  45. Dual regulation of cofilin activity by LIM kinase and Slingshot-1L phosphatase controls platelet-derived growth factor-induced migration of human aortic smooth muscle cells.
    Circ Res. 2008 Feb 29;102(4):432-8 PMID: 18096821
  46. Cell migration: integrating signals from front to back.
    Science. 2003 Dec 5;302(5651):1704-9 PMID: 14657486
  47. Role of formins in actin assembly: nucleation and barbed-end association.
    Science. 2002 Jul 26;297(5581):612-5 PMID: 12052901
  48. Epidermal growth factor receptor transactivation by angiotensin II requires reactive oxygen species in vascular smooth muscle cells.
    Arterioscler Thromb Vasc Biol. 2001 Apr;21(4):489-95 PMID: 11304462
  49. A pathway of neuregulin-induced activation of cofilin-phosphatase Slingshot and cofilin in lamellipodia.
    J Cell Biol. 2004 May 24;165(4):465-71 PMID: 15159416
  50. Nox1-dependent superoxide production controls colon adenocarcinoma cell migration.
    Biochim Biophys Acta. 2008 Jan;1783(1):23-33 PMID: 18023288
  51. The serine phosphatases PP1 and PP2A associate with and activate the actin-binding protein cofilin in human T lymphocytes.
    Eur J Immunol. 2000 Dec;30(12):3422-31 PMID: 11093160
  52. The expression of the NADPH oxidase subunit p22phox is regulated by a redox-sensitive pathway in endothelial cells.
    Free Radic Biol Med. 2005 Mar 1;38(5):616-30 PMID: 15683718
  53. Reactive oxygen species regulate F-actin dynamics in neuronal growth cones and neurite outgrowth.
    J Neurochem. 2009 Feb;108(3):644-61 PMID: 19054285
  54. Angiotensin receptors: a new role in cancer?
    Trends Endocrinol Metab. 2005 Sep;16(7):293-9 PMID: 16061390
  55. Nox1 mediates basic fibroblast growth factor-induced migration of vascular smooth muscle cells.
    Arterioscler Thromb Vasc Biol. 2007 Aug;27(8):1736-43 PMID: 17541028
  56. The cofilin pathway in breast cancer invasion and metastasis.
    Nat Rev Cancer. 2007 Jun;7(6):429-40 PMID: 17522712
  57. Life at the leading edge: the formation of cell protrusions.
    Annu Rev Cell Biol. 1993;9:411-44 PMID: 8280467
Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1939-4586
DOI
10.1091/mbc.e09-02-0131
Published
2009-06-00
Epub
2009-00-01
Pages
2650-60
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC2688545
Subset
IM
Grants
NIGMS NIH HHS · R01 GM044428 · United States
NHLBI NIH HHS · R01 HL048008 · United States
NIGMS NIH HHS · GM44428 · United States
NHLBI NIH HHS · HL48008 · United States
External Links
PubMed source DOI: 10.1091/mbc.e09-02-0131 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2