Cell 2001,
PMID: 11779461
Habas, R; Kato, Y; He, X
Wnt signaling via the Frizzled (Fz) receptor controls cell polarity and movement during development, but the molecular nature of Wnt/Fz polarity signal transduction remains poorly defined. Here we report that in human cells and during Xenopus embryogenesis, Wnt/Fz signaling activates the small GTPase Rho, a key regulator of cytoskeleton architecture. Wnt/Fz activation of Rho requires the cytoplasmic protein Dishevelled (Dvl) and a novel Formin homology protein Daam1. Daam1 binds to both Dvl and Rho, and mediates Wnt-induced Dvl-Rho complex formation. Inhibition or depletion of Daam1 prevents Wnt/Fz activation of Rho and of Xenopus gastrulation, but not of beta-catenin signaling. Our study illustrates a molecular pathway from Wnt/Fz signaling to Rho activation in cell polarity signal transduction.
Document information provided by NCBI PubMed
Text Mining Data
Rho → Daam1: "
Wnt/Frizzled activation of
Rho regulates vertebrate gastrulation and
requires a novel Formin homology protein
Daam1
"
Wnt/Frizzled → Rho: "
Wnt/Frizzled activation of Rho regulates vertebrate gastrulation and requires a novel Formin homology protein Daam1
"
Wnt/Frizzled → Daam1: "
Wnt/Frizzled activation of Rho regulates vertebrate gastrulation and requires a novel Formin homology protein Daam1
"
Rho → Wnt/Fz: "
Here we report that in human cells and during Xenopus embryogenesis, Wnt/Fz signaling activates the small GTPase Rho , a key regulator of cytoskeleton architecture
"
Rho → Daam1: "
Wnt/Fz activation of Rho requires the cytoplasmic protein Dishevelled ( Dvl ) and a novel Formin homology protein Daam1
"
Rho → Dishevelled ( Dvl ): "
Wnt/Fz activation of Rho requires the cytoplasmic protein Dishevelled ( Dvl ) and a novel Formin homology protein Daam1
"
Wnt/Fz → Rho: "
Wnt/Fz activation of Rho requires the cytoplasmic protein Dishevelled ( Dvl ) and a novel Formin homology protein Daam1
"
Wnt/Fz → Daam1: "
Wnt/Fz activation of Rho requires the cytoplasmic protein Dishevelled ( Dvl ) and a novel Formin homology protein Daam1
"
Wnt/Fz → Dishevelled ( Dvl ): "
Wnt/Fz activation of Rho requires the cytoplasmic protein Dishevelled ( Dvl ) and a novel Formin homology protein Daam1
"
Dvl-Rho → Wnt: "
Daam1 binds to both Dvl and Rho, and mediates Wnt induced Dvl-Rho complex formation
"
Dvl-Rho → Daam1: "
Daam1 binds to both Dvl and Rho, and mediates Wnt induced Dvl-Rho complex formation
"
Dvl-Rho → Wnt: "
Daam1 binds to both Dvl and Rho, and mediates Wnt induced Dvl-Rho complex formation
"
Dvl-Rho → Daam1: "
Daam1 binds to both Dvl and Rho, and mediates Wnt induced Dvl-Rho complex formation
"
Wnt/Fz → Rho: "
Inhibition or depletion of Daam1 prevents Wnt/Fz activation of Rho and of Xenopus gastrulation, but not of beta-catenin signaling
"
Wnt/Fz → beta-catenin: "
Inhibition or depletion of Daam1 prevents Wnt/Fz activation of Rho and of Xenopus gastrulation, but not of beta-catenin signaling
"
Manually curated Databases
-
OpenBEL Selventa BEL large corpus:
Complex of DVL2-RHOA
→
WNT1
(increases)
Evidence: Since Daam1 binds to Dvl and RhoA, we tested whether Daam1 forms a ternary complex with Dvl and RhoA. We immunoprecipitated the endogenous RhoA from 293T cells treated with or without Wnt-1 CM. Strikingly, we found that the endogenous Dvl protein is associated with RhoA only upon Wnt stimulation (Figure 2G).
-
OpenBEL Selventa BEL large corpus:
RAC1
→
WNT1
(increases, WNT1 Activity)
Evidence: Surprisingly, Wnt-1, which has been studied primarily in ?-catenin signaling, activates RhoA and Rac, but not Cdc42 (Figure 1B).
-
OpenBEL Selventa BEL large corpus:
RHOA
→
WNT1
(increases, WNT1 Activity)
Evidence: Surprisingly, Wnt-1, which has been studied primarily in ?-catenin signaling, activates RhoA and Rac, but not Cdc42 (Figure 1B).
-
OpenBEL Selventa BEL large corpus:
RHOA
→
DAAM1
(increases, DAAM1 Activity)
Evidence: Rho, Rac, and Cdc42 elicit distinct morphological changes in cultured mammalian cells (Hall, 1998). Specifically, Rho activation induces stress fiber formation. We found that N-Daam1 disrupts, whereas C-Daam1 enhances, the formation of actin stress fibers (Figure 4A). Thus, the cell biological assay is consistent with the biochemical evidence that Daam1 regulates RhoA activity.
-
OpenBEL Selventa BEL large corpus:
RHOA
→
DAAM1
(increases, DAAM1 Activity)
Evidence: We also employed double-strand (ds) RNA mediated interference (RNAi) (Elbashir et al., 2001) to deplete endogenous Daam1 protein. The ds RNAi oligo for Daam1 reduces the protein level of Daam1, but not of RhoA, ?-catenin (Figure 3C) or Dvl2 (not shown). Importantly, the RNAi oligo inhibits RhoA activation by Wnt-1, Fz, or Dvl, but not by Ephexin (Figure 3C). A control ds RNAi oligo has no effect on Daam1 or RhoA protein level or RhoA activation (Figure 3C). Thus, Daam1 is essential for Wnt/Fz/Dv...
-
OpenBEL Selventa BEL large corpus:
RHOA
→
DVL2
(increases, DVL2 Activity)
Evidence: Since Daam1 binds to Dvl and RhoA, we tested whether Daam1 forms a ternary complex with Dvl and RhoA. We immunoprecipitated the endogenous RhoA from 293T cells treated with or without Wnt-1 CM. Strikingly, we found that the endogenous Dvl protein is associated with RhoA only upon Wnt stimulation (Figure 2G).
-
OpenBEL Selventa BEL large corpus:
RAC1
→
FZD1
(increases, FZD1 Activity)
Evidence: Fz1 also activates Rac weakly but not Cdc42 (Figure 1A), as detected via an analogous assay using GST-PBD (p21 binding domain) that recognizes GTP-bound Rac or Cdc42 (Benard et al. 1999 and Akasaki et al. 1999).
-
OpenBEL Selventa BEL large corpus:
RHOA
→
FZD1
(increases, FZD1 Activity)
Evidence: Fz1 similarly activates RhoA (Figure 1A) and beta-catenin signaling (Yang-Snyder et al., 1996)
-
IRef Hprd Interaction:
DVL2
—
DAAM1
(in vivo)
-
IRef Hprd Interaction:
RHOA
—
DAAM1
(in vitro)
-
IRef Hprd Interaction:
RHOA
—
DAAM1
(in vivo)
-
IRef Hprd Interaction:
DAAM1
—
DVL1
(in vitro)
-
IRef Hprd Interaction:
DAAM1
—
DVL1
(in vivo)
-
IRef Hprd Interaction:
DAAM1
—
DVL1
(two hybrid)
-
NCI Pathway Database Noncanonical Wnt signaling pathway:
None
→
RHOA/GTP complex (RHOA)
(modification, collaborate)
Evidence: mutant phenotype
-
NCI Pathway Database Noncanonical Wnt signaling pathway:
None
→
DVL/DAAM1 complex (DVL3_DVL1_DVL2-DAAM1)
(modification, collaborate)
Evidence: mutant phenotype
-
NCI Pathway Database Noncanonical Wnt signaling pathway:
None
→
RHOA/GDP complex (RHOA)
(modification, collaborate)
Evidence: mutant phenotype
-
NCI Pathway Database Noncanonical Wnt signaling pathway:
None
→
None
(modification, collaborate)
Evidence: mutant phenotype
-
NCI Pathway Database Noncanonical Wnt signaling pathway:
RHOA/GTP complex (RHOA)
→
RHOA/GDP complex (RHOA)
(modification, collaborate)
Evidence: mutant phenotype
-
NCI Pathway Database Noncanonical Wnt signaling pathway:
RHOA/GTP complex (RHOA)
→
None
(modification, collaborate)
Evidence: mutant phenotype
-
NCI Pathway Database Noncanonical Wnt signaling pathway:
DVL/DAAM1 complex (DVL3_DVL1_DVL2-DAAM1)
→
RHOA/GDP complex (RHOA)
(modification, activates)
Evidence: mutant phenotype
-
NCI Pathway Database Noncanonical Wnt signaling pathway:
DVL/DAAM1 complex (DVL3_DVL1_DVL2-DAAM1)
→
None
(modification, activates)
Evidence: mutant phenotype
-
NCI Pathway Database Noncanonical Wnt signaling pathway:
RHOA/GDP complex (RHOA)
→
None
(modification, collaborate)
Evidence: mutant phenotype
-
NCI Pathway Database Noncanonical Wnt signaling pathway:
DVL (DVL3/DVL1/DVL2)
→
DAAM1 (DAAM1)
(modification, collaborate)
Evidence: physical interaction
-
NCI Pathway Database Noncanonical Wnt signaling pathway:
DVL (DVL3/DVL1/DVL2)
→
DVL/DAAM1 complex (DVL2-DAAM1)
(modification, collaborate)
Evidence: physical interaction
-
NCI Pathway Database Noncanonical Wnt signaling pathway:
DAAM1 (DAAM1)
→
DVL/DAAM1 complex (DVL2-DAAM1)
(modification, collaborate)
Evidence: physical interaction
-
Reactome Reaction:
DVL2
→
RAC1
(reaction)
-
Reactome Reaction:
DVL2
→
RHOA
(indirect_complex)
-
Reactome Reaction:
RHOA
→
DAAM1
(indirect_complex)
-
Reactome Reaction:
RHOA
→
DAAM1
(reaction)
-
Reactome Reaction:
DVL2
→
DAAM1
(reaction)
-
Reactome Reaction:
DVL2
→
DAAM1
(direct_complex)
-
Reactome Reaction:
DVL2
→
RAC1
(indirect_complex)
-
Reactome Reaction:
DVL2
→
RHOA
(reaction)
In total, 13 gene pairs are associated to this article in curated databases