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PMID: 17606906 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Src phosphorylation of cortactin enhances actin assembly.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 104 ·No. 29 ·2007-07-17 ·Pages 11933-8

Tehrani S, Tomasevic N, Weed S, Sakowicz R, Cooper JA

Abstract

Src kinase mediates growth factor signaling and causes oncogenic transformation, which includes dramatic changes in the actin cytoskeleton, cell shape, and motility. Cortactin was discovered as a substrate for Src. How phosphorylation of cortactin can enhance actin assembly is unknown. Here, using an actin assembly system reconstituted from purified components, we demonstrate for the first time a biochemical mechanism by which Src phosphorylation of cortactin affects actin assembly. The adaptor Nck is an important component of the system, linking phosphorylated cortactin with neuronal WASp (N-WASp) and WASp-interacting protein (WIP) to activate Arp2/3 complex.

MeSH Terms
Actin-Related Protein 2-3 Complex/metabolism Actins/chemistry,metabolism Adaptor Proteins, Signal Transducing Animals Carrier Proteins/metabolism Cattle Cortactin/chemistry,metabolism Humans Oncogene Proteins/metabolism Phosphorylation Protein Binding Protein Structure, Quaternary Protein Transport Proto-Oncogene Proteins pp60(c-src)/metabolism Swine Tyrosine/metabolism Wiskott-Aldrich Syndrome Protein, Neuronal/metabolism
Chemicals
Actin-Related Protein 2-3 Complex Actins Adaptor Proteins, Signal Transducing Carrier Proteins Cortactin Nck protein Oncogene Proteins Wiskott-Aldrich Syndrome Protein, Neuronal Tyrosine Proto-Oncogene Proteins pp60(c-src)
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Tehrani Shandiz
Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA. tehranis@medicine.wustl.edu
Tomasevic Nenad
Weed Scott
Sakowicz Roman
Cooper John A
References (51)
51 references, click to expand
  1. A generic protein purification method for protein complex characterization and proteome exploration.
    Nat Biotechnol. 1999 Oct;17(10):1030-2 PMID: 10504710
  2. Cortactin regulates cell migration through activation of N-WASP.
    J Cell Sci. 2005 Jan 1;118(Pt 1):79-87 PMID: 15585574
  3. Molecular mechanisms of invadopodium formation: the role of the N-WASP-Arp2/3 complex pathway and cofilin.
    J Cell Biol. 2005 Jan 31;168(3):441-52 PMID: 15684033
  4. A neural Wiskott-Aldrich Syndrome protein-mediated pathway for localized activation of actin polymerization that is regulated by cortactin.
    J Biol Chem. 2005 Feb 18;280(7):5836-42 PMID: 15579908
  5. Actin dynamics: growth from dendritic branches.
    Curr Biol. 2005 May 10;15(9):R346-57 PMID: 15886095
  6. Cellular invasion by Staphylococcus aureus reveals a functional link between focal adhesion kinase and cortactin in integrin-mediated internalisation.
    J Cell Sci. 2005 May 15;118(Pt 10):2189-200 PMID: 15855238
  7. Cortactin promotes cell motility by enhancing lamellipodial persistence.
    Curr Biol. 2005 Jul 26;15(14):1276-85 PMID: 16051170
  8. Divergent roles of c-Src in controlling platelet-derived growth factor-dependent signaling in fibroblasts.
    Mol Biol Cell. 2005 Nov;16(11):5418-32 PMID: 16135530
  9. Caenorhabditis elegans WASP-interacting protein homologue WIP-1 is involved in morphogenesis through maintenance of WSP-1 protein levels.
    Biochem Biophys Res Commun. 2006 Feb 10;340(2):709-17 PMID: 16378591
  10. Dynamic interactions of cortactin and membrane type 1 matrix metalloproteinase at invadopodia: defining the stages of invadopodia formation and function.
    Cancer Res. 2006 Mar 15;66(6):3034-43 PMID: 16540652
  11. Podosomes as smart regulators of cellular adhesion.
    Eur J Cell Biol. 2006 Apr;85(3-4):191-4 PMID: 16546561
  12. Invadopodia and podosomes in tumor invasion.
    Eur J Cell Biol. 2006 Apr;85(3-4):213-8 PMID: 16546563
  13. Co-localization of cortactin and phosphotyrosine identifies active invadopodia in human breast cancer cells.
    Exp Cell Res. 2006 May 1;312(8):1240-53 PMID: 16442522
  14. A complex of Wiskott-Aldrich syndrome protein with mammalian verprolins plays an important role in monocyte chemotaxis.
    J Immunol. 2006 Jun 1;176(11):6576-85 PMID: 16709815
  15. Harnessing actin dynamics for clathrin-mediated endocytosis.
    Nat Rev Mol Cell Biol. 2006 Jun;7(6):404-14 PMID: 16723976
  16. Requirement of Nck adaptors for actin dynamics and cell migration stimulated by platelet-derived growth factor B.
    Proc Natl Acad Sci U S A. 2006 Jun 20;103(25):9536-41 PMID: 16769879
  17. Cortactin has an essential and specific role in osteoclast actin assembly.
    Mol Biol Cell. 2006 Jul;17(7):2882-95 PMID: 16611741
  18. Invadopodia: specialized cell structures for cancer invasion.
    Clin Exp Metastasis. 2006;23(2):97-105 PMID: 16830222
  19. Endothelial cell cortactin coordinates intercellular adhesion molecule-1 clustering and actin cytoskeleton remodeling during polymorphonuclear leukocyte adhesion and transmigration.
    J Immunol. 2006 Nov 1;177(9):6440-9 PMID: 17056576
  20. WIP is a chaperone for Wiskott-Aldrich syndrome protein (WASP).
    Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):926-31 PMID: 17213309
  21. Influence of the C terminus of Wiskott-Aldrich syndrome protein (WASp) and the Arp2/3 complex on actin polymerization.
    Biochemistry. 1999 Nov 16;38(46):15212-22 PMID: 10563804
  22. Src is required for cell migration and shape changes induced by fibroblast growth factor 1.
    Oncogene. 1999 Nov 18;18(48):6700-6 PMID: 10597276
  23. Cortactin localization to sites of actin assembly in lamellipodia requires interactions with F-actin and the Arp2/3 complex.
    J Cell Biol. 2000 Oct 2;151(1):29-40 PMID: 11018051
  24. Cortactin promotes and stabilizes Arp2/3-induced actin filament network formation.
    Curr Biol. 2001 Mar 6;11(5):370-4 PMID: 11267876
  25. WIP regulates N-WASP-mediated actin polymerization and filopodium formation.
    Nat Cell Biol. 2001 May;3(5):484-91 PMID: 11331876
  26. Nck and phosphatidylinositol 4,5-bisphosphate synergistically activate actin polymerization through the N-WASP-Arp2/3 pathway.
    J Biol Chem. 2001 Jul 13;276(28):26448-52 PMID: 11340081
  27. Cortactin potentiates bone metastasis of breast cancer cells.
    Cancer Res. 2001 Sep 15;61(18):6906-11 PMID: 11559568
  28. CR16 forms a complex with N-WASP in brain and is a novel member of a conserved proline-rich actin-binding protein family.
    Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11306-11 PMID: 11553796
  29. Interaction of cortactin and N-WASp with Arp2/3 complex.
    Curr Biol. 2002 Aug 6;12(15):1270-8 PMID: 12176354
  30. Structure of the N-WASP EVH1 domain-WIP complex: insight into the molecular basis of Wiskott-Aldrich Syndrome.
    Cell. 2002 Nov 15;111(4):565-76 PMID: 12437929
  31. Cortactin interacts with WIP in regulating Arp2/3 activation and membrane protrusion.
    Curr Biol. 2003 Mar 4;13(5):384-93 PMID: 12620186
  32. A Cortactin-CD2-associated protein (CD2AP) complex provides a novel link between epidermal growth factor receptor endocytosis and the actin cytoskeleton.
    J Biol Chem. 2003 Jun 13;278(24):21805-13 PMID: 12672817
  33. Podosomes: adhesion hot-spots of invasive cells.
    Trends Cell Biol. 2003 Jul;13(7):376-85 PMID: 12837608
  34. Cortactin tyrosine phosphorylation requires Rac1 activity and association with the cortical actin cytoskeleton.
    Mol Biol Cell. 2003 Aug;14(8):3216-29 PMID: 12925758
  35. How capping protein binds the barbed end of the actin filament.
    Curr Biol. 2003 Sep 2;13(17):1531-7 PMID: 12956956
  36. Imaging sites of N-wasp activity in lamellipodia and invadopodia of carcinoma cells.
    Curr Biol. 2004 Apr 20;14(8):697-703 PMID: 15084285
  37. Erk/Src phosphorylation of cortactin acts as a switch on-switch off mechanism that controls its ability to activate N-WASP.
    Mol Cell Biol. 2004 Jun;24(12):5269-80 PMID: 15169891
  38. Toca-1 mediates Cdc42-dependent actin nucleation by activating the N-WASP-WIP complex.
    Cell. 2004 Jul 23;118(2):203-16 PMID: 15260990
  39. Cellular localization of activated N-WASP using a conformation-sensitive antibody.
    Cell Motil Cytoskeleton. 2004 Oct;59(2):141-52 PMID: 15362118
  40. Cortactin associates with N-cadherin adhesions and mediates intercellular adhesion strengthening in fibroblasts.
    J Cell Sci. 2004 Oct 1;117(Pt 21):5117-31 PMID: 15383621
  41. The road to Src.
    Oncogene. 2004 Oct 18;23(48):7910-7 PMID: 15489909
  42. Rous sarcoma virus-transformed fibroblasts adhere primarily at discrete protrusions of the ventral membrane called podosomes.
    Exp Cell Res. 1985 Jul;159(1):141-57 PMID: 2411576
  43. Proteolytic activity of specialized surface protrusions formed at rosette contact sites of transformed cells.
    J Exp Zool. 1989 Aug;251(2):167-85 PMID: 2549171
  44. Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice.
    Cell. 1991 Feb 22;64(4):693-702 PMID: 1997203
  45. Identification and characterization of a novel cytoskeleton-associated pp60src substrate.
    Mol Cell Biol. 1991 Oct;11(10):5113-24 PMID: 1922035
  46. c-Src regulates the simultaneous rearrangement of actin cytoskeleton, p190RhoGAP, and p120RasGAP following epidermal growth factor stimulation.
    J Cell Biol. 1995 Jul;130(2):355-68 PMID: 7542246
  47. p80/85 cortactin associates with the Src SH2 domain and colocalizes with v-Src in transformed cells.
    J Biol Chem. 1995 Nov 3;270(44):26613-8 PMID: 7592885
  48. The Wiskott-Aldrich syndrome protein-interacting protein (WIP) binds to the adaptor protein Nck.
    J Biol Chem. 1998 Aug 14;273(33):20992-5 PMID: 9694849
  49. The interaction between N-WASP and the Arp2/3 complex links Cdc42-dependent signals to actin assembly.
    Cell. 1999 Apr 16;97(2):221-31 PMID: 10219243
  50. Regulation of endothelial cell myosin light chain kinase by Rho, cortactin, and p60(src).
    Am J Physiol. 1999 Jun;276(6 Pt 1):L989-98 PMID: 10362724
  51. Activation of the CDC42 effector N-WASP by the Shigella flexneri IcsA protein promotes actin nucleation by Arp2/3 complex and bacterial actin-based motility.
    J Cell Biol. 1999 Sep 20;146(6):1319-32 PMID: 10491394
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0701077104
Email
tehranis@medicine.wustl.edu
Published
2007-07-17
Epub
2007-00-02
Pages
11933-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1924558
Subset
IM
Grants
NIGMS NIH HHS · R01 GM038542 · United States
NIGMS NIH HHS · R01 GM038542-20 · United States
NIGMS NIH HHS · T32 GM007200 · United States
NIGMS NIH HHS · GM38542 · United States
NIGMS NIH HHS · GM07200 · United States
External Links
PubMed source DOI: 10.1073/pnas.0701077104 PMC Full Text View journal details
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