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

  1. Weikang Tao1,
  2. Diane Pennica2,
  3. Lifeng Xu1,
  4. Robert F. Kalejta1, and
  5. Arnold J. Levine3,4
  1. 1Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA; 2Department of Molecular Oncology, Genentech, Inc., South San Francisco, California 94080, USA; 3The Rockefeller University, New York, New York 10021-6399, USA

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.

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Footnotes

  • ↵4 Corresponding author.

  • E-MAIL alevine{at}rockvax.rockefeller.edu; FAX (212) 327–8900.

  • Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.894301.

    • Received March 9, 2001.
    • Accepted May 22, 2001.
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  1. doi: 10.1101/gad.894301 Genes & Dev. 15: 1796-1807 Cold Spring Harbor Laboratory Press

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