Home LiteratureArticle Details
PMID: 11459829 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Wrch-1, a novel member of the Rho gene family that is regulated by Wnt-1.

Genes & development ·Vol. 15 ·No. 14 ·2001-07-15 ·Pages 1796-807

Tao W, Pennica D, Xu L, Kalejta RF, Levine AJ

Abstract

We report the isolation and cloning of the Wrch-1 (Wnt-1 responsive Cdc42 homolog) cDNA. Wrch-1 is a novel gene whose mRNA level increases in response to Wnt-1 signaling in Wnt-1 transformed cells, Wnt-1 transgene induced mouse mammary tumors, and Wnt-1 retrovirus infected cells. Wrch-1 encodes a homolog of the Rho family of GTPases. It shares 57% amino acid sequence identity with Cdc42, but possesses a unique N-terminal domain that contains several putative PXXP SH3-binding motifs. Like Cdc42, Wrch-1 can activate PAK-1 and JNK-1, and induce filopodium formation and stress fiber dissolution. Active Wrch-1 stimulates quiescent cells to reenter the cell cycle. Moreover, overexpression of Wrch-1 phenocopies Wnt-1 in morphological transformation of mouse mammary epithelial cells. Taken together, Wrch-1 could mediate the effects of Wnt-1 signaling in the regulation of cell morphology, cytoskeletal organization, and cell proliferation.

MeSH Terms
Amino Acid Sequence Animals Cloning, Molecular GTP-Binding Proteins/genetics Ganglia, Spinal Gene Expression Regulation Humans Mice/embryology Mitogen-Activated Protein Kinase 8 Mitogen-Activated Protein Kinases/metabolism Molecular Sequence Data Multigene Family Protein Serine-Threonine Kinases/metabolism Proto-Oncogene Proteins/metabolism Sequence Homology, Amino Acid Signal Transduction Spinal Cord Tissue Distribution Trigeminal Ganglion Wnt Proteins Wnt1 Protein Zebrafish Proteins p21-Activated Kinases rho GTP-Binding Proteins
Chemicals
Proto-Oncogene Proteins WNT1 protein, human Wnt Proteins Wnt1 Protein Wnt1 protein, mouse Zebrafish Proteins PAK1 protein, human Pak1 protein, mouse Protein Serine-Threonine Kinases p21-Activated Kinases Mitogen-Activated Protein Kinase 8 Mitogen-Activated Protein Kinases GTP-Binding Proteins RHOU protein, human rho GTP-Binding Proteins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Tao W
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
Pennica D
Xu L
Kalejta R F
Levine A J
References (57)
57 references, click to expand
  1. Mechanism and function of signal transduction by the Wnt/beta-catenin and Wnt/Ca2+ pathways.
    Oncogene. 1999 Dec 20;18(55):7860-72 PMID: 10630639
  2. An essential role for Rac in Ras transformation.
    Nature. 1995 Mar 30;374(6521):457-9 PMID: 7700355
  3. Wnt signaling in oncogenesis and embryogenesis--a look outside the nucleus.
    Science. 2000 Mar 3;287(5458):1606-9 PMID: 10733430
  4. The Wnt/Ca2+ pathway: a new vertebrate Wnt signaling pathway takes shape.
    Trends Genet. 2000 Jul;16(7):279-83 PMID: 10858654
  5. Wnt signaling and cancer.
    Genes Dev. 2000 Aug 1;14(15):1837-51 PMID: 10921899
  6. Interaction of Wnt and a Frizzled homologue triggers G-protein-linked phosphatidylinositol signalling.
    Nature. 1997 Nov 27;390(6658):410-3 PMID: 9389482
  7. Cdc42 and Rac1 induce integrin-mediated cell motility and invasiveness through PI(3)K.
    Nature. 1997 Dec 11;390(6660):632-6 PMID: 9403696
  8. Wnt signaling: a common theme in animal development.
    Genes Dev. 1997 Dec 15;11(24):3286-305 PMID: 9407023
  9. Signal transduction by the Wnt family of ligands.
    Biochem J. 1998 Jan 15;329 ( Pt 2):209-23 PMID: 9425102
  10. Rho GTPases and the actin cytoskeleton.
    Science. 1998 Jan 23;279(5350):509-14 PMID: 9438836
  11. A simplified system for generating recombinant adenoviruses.
    Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2509-14 PMID: 9482916
  12. Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia.
    Cell. 1995 Apr 7;81(1):53-62 PMID: 7536630
  13. A role for Rac in Tiam1-induced membrane ruffling and invasion.
    Nature. 1995 May 25;375(6529):338-40 PMID: 7753201
  14. The small GTP-binding proteins Rac1 and Cdc42 regulate the activity of the JNK/SAPK signaling pathway.
    Cell. 1995 Jun 30;81(7):1137-46 PMID: 7600581
  15. Selective activation of the JNK signaling cascade and c-Jun transcriptional activity by the small GTPases Rac and Cdc42Hs.
    Cell. 1995 Jun 30;81(7):1147-57 PMID: 7600582
  16. An essential role for Rho, Rac, and Cdc42 GTPases in cell cycle progression through G1.
    Science. 1995 Sep 1;269(5228):1270-2 PMID: 7652575
  17. Rho family members: activators of MAP kinase cascades.
    Cell. 1995 Aug 25;82(4):527-9 PMID: 7664330
  18. A novel serine kinase activated by rac1/CDC42Hs-dependent autophosphorylation is related to PAK65 and STE20.
    EMBO J. 1995 Sep 1;14(17):4385 PMID: 7556080
  19. Evidence for the involvement of the Wnt 2 gene in human colorectal cancer.
    Oncogene. 1996 Jan 4;12(1):153-8 PMID: 8552386
  20. Functional interaction of beta-catenin with the transcription factor LEF-1.
    Nature. 1996 Aug 15;382(6592):638-42 PMID: 8757136
  21. Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC.
    Science. 1997 Mar 21;275(5307):1787-90 PMID: 9065402
  22. Stabilization of beta-catenin by genetic defects in melanoma cell lines.
    Science. 1997 Mar 21;275(5307):1790-2 PMID: 9065403
  23. Modulation of embryonic intracellular Ca2+ signaling by Wnt-5A.
    Dev Biol. 1997 Feb 1;182(1):114-20 PMID: 9073455
  24. The role of RhoA in tissue polarity and Frizzled signalling.
    Nature. 1997 May 15;387(6630):292-5 PMID: 9153394
  25. Cdc42 regulates anchorage-independent growth and is necessary for Ras transformation.
    Mol Cell Biol. 1997 Jun;17(6):3449-58 PMID: 9154844
  26. Modulation of cell death in yeast by the Bcl-2 family of proteins.
    J Biol Chem. 1997 Jun 13;272(24):15547-52 PMID: 9182591
  27. The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation.
    Cell. 1997 Jul 11;90(1):181-92 PMID: 9230313
  28. Rho GTPases and signaling networks.
    Genes Dev. 1997 Sep 15;11(18):2295-322 PMID: 9308960
  29. Identification of connexin43 as a functional target for Wnt signalling.
    J Cell Sci. 1998 Jun;111 ( Pt 12):1741-9 PMID: 9601103
  30. Somatic mutations of the beta-catenin gene are frequent in mouse and human hepatocellular carcinomas.
    Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8847-51 PMID: 9671767
  31. Identification of c-MYC as a target of the APC pathway.
    Science. 1998 Sep 4;281(5382):1509-12 PMID: 9727977
  32. Wnt5a cloning, expression, and up-regulation in human primary breast cancers.
    Clin Cancer Res. 1995 Feb;1(2):215-22 PMID: 9815976
  33. WISP genes are members of the connective tissue growth factor family that are up-regulated in wnt-1-transformed cells and aberrantly expressed in human colon tumors.
    Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14717-22 PMID: 9843955
  34. Cellular mechanisms of wingless/Wnt signal transduction.
    Curr Top Dev Biol. 1999;43:153-90 PMID: 9891886
  35. Target genes of beta-catenin-T cell-factor/lymphoid-enhancer-factor signaling in human colorectal carcinomas.
    Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1603-8 PMID: 9990071
  36. The human F box protein beta-Trcp associates with the Cul1/Skp1 complex and regulates the stability of beta-catenin.
    Oncogene. 1999 Jan 28;18(4):849-54 PMID: 10023660
  37. The oncogenic activation of beta-catenin.
    Curr Opin Genet Dev. 1999 Feb;9(1):15-21 PMID: 10072352
  38. An integral membrane green fluorescent protein marker, Us9-GFP, is quantitatively retained in cells during propidium iodide-based cell cycle analysis by flow cytometry.
    Exp Cell Res. 1999 Apr 10;248(1):322-8 PMID: 10094838
  39. A common human skin tumour is caused by activating mutations in beta-catenin.
    Nat Genet. 1999 Apr;21(4):410-3 PMID: 10192393
  40. Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells.
    Nature. 1999 Apr 1;398(6726):422-6 PMID: 10201372
  41. The C-terminal domain of armadillo binds to hypophosphorylated teashirt to modulate wingless signalling in Drosophila.
    EMBO J. 1999 Apr 15;18(8):2208-17 PMID: 10205174
  42. The Wnt/Wg signal transducer beta-catenin controls fibronectin expression.
    Mol Cell Biol. 1999 Aug;19(8):5576-87 PMID: 10409747
  43. Genomic analysis of metastasis reveals an essential role for RhoC.
    Nature. 2000 Aug 3;406(6795):532-5 PMID: 10952316
  44. Identification of a mouse homolog of the human BTEB2 transcription factor as a beta-catenin-independent Wnt-1-responsive gene.
    Mol Cell Biol. 2001 Jan;21(2):562-74 PMID: 11134343
  45. Mode of proviral activation of a putative mammary oncogene (int-1) on mouse chromosome 15.
    Nature. 1984 Jan 12-18;307(5947):131-6 PMID: 6318122
  46. Expression of the proto-oncogene int-1 is restricted to postmeiotic male germ cells and the neural tube of mid-gestational embryos.
    Cell. 1987 Jul 3;50(1):89-95 PMID: 3594566
  47. Expression of the int-1 gene in transgenic mice is associated with mammary gland hyperplasia and adenocarcinomas in male and female mice.
    Cell. 1988 Nov 18;55(4):619-25 PMID: 3180222
  48. The Wnt-1 (int-1) proto-oncogene is required for development of a large region of the mouse brain.
    Cell. 1990 Sep 21;62(6):1073-85 PMID: 2205396
  49. The ras-related gene rhoB is an immediate-early gene inducible by v-Fps, epidermal growth factor, and platelet-derived growth factor in rat fibroblasts.
    Mol Cell Biol. 1991 Jul;11(7):3682-90 PMID: 1710770
  50. The mouse Wnt-1 gene can act via a paracrine mechanism in transformation of mammary epithelial cells.
    Mol Cell Biol. 1992 Jan;12(1):321-8 PMID: 1530877
  51. Mutational analysis of mouse Wnt-1 identifies two temperature-sensitive alleles and attributes of Wnt-1 protein essential for transformation of a mammary cell line.
    Mol Biol Cell. 1992 May;3(5):521-33 PMID: 1535241
  52. Growth-regulated expression of rhoG, a new member of the ras homolog gene family.
    Mol Cell Biol. 1992 Jul;12(7):3138-48 PMID: 1620121
  53. Activity of Wnt-1 as a transmembrane protein.
    Genes Dev. 1993 Nov;7(11):2181-93 PMID: 8224845
  54. A brain serine/threonine protein kinase activated by Cdc42 and Rac1.
    Nature. 1994 Jan 6;367(6458):40-6 PMID: 8107774
  55. Deregulated expression of E2F-1 induces S-phase entry and leads to apoptosis.
    Mol Cell Biol. 1994 Dec;14(12):8166-73 PMID: 7969153
  56. The Ras-related protein Cdc42Hs and bradykinin promote formation of peripheral actin microspikes and filopodia in Swiss 3T3 fibroblasts.
    Mol Cell Biol. 1995 Apr;15(4):1942-52 PMID: 7891688
  57. WISP-1 is a Wnt-1- and beta-catenin-responsive oncogene.
    Genes Dev. 2000 Mar 1;14(5):585-95 PMID: 10716946
Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.894301
Published
2001-07-15
Pages
1796-807
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC312736
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.894301 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