Wrch-1, a novel member of the Rho gene family that is regulated by Wnt-1.
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.
Tao
W
W
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
Pennica
D
D
Xu
L
L
Kalejta
R F
RF
Levine
A J
AJ
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D019204:GTP-Binding Proteins / Q000235:genetics*; D005727:Ganglia, Spinal; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice / Q000196:embryology; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D005810:Multigene Family; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013116:Spinal Cord; D014018:Tissue Distribution; D012668:Trigeminal Ganglion; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; D054462:p21-Activated Kinases; D020741:rho GTP-Binding Proteins
D011518:Proto-Oncogene Proteins; C495247:WNT1 protein, human; D051153:Wnt Proteins; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D029961:Zebrafish Proteins; C515903:PAK1 protein, human; C515905:Pak1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins; C432668:RHOU protein, human; D020741:rho GTP-Binding Proteins