Reactome | DAAM1 recruits GTP-bound RHOA

DAAM1 recruits GTP-bound RHOA

Stable Identifier

R-HSA-3858495

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

Locations in the PathwayBrowser

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Signal Transduction (Homo sapiens)

- Signaling by Rho GTPases, Miro GTPases and RHOBTB3 (Homo sapiens)
  - Signaling by Rho GTPases (Homo sapiens)
    - RHO GTPase Effectors (Homo sapiens)
      - RHO GTPases Activate Formins (Homo sapiens)
        
        DAAM1 recruits GTP-bound RHOA (Homo sapiens)
- Signaling by WNT (Homo sapiens)
  - Beta-catenin independent WNT signaling (Homo sapiens)
    - PCP/CE pathway (Homo sapiens)
      - DAAM1 recruits GTP-bound RHOA (Homo sapiens)

General

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Activated DAAM1 recruits RHOA to the DVL complex in a WNT-dependent manner. Activated DAAM1 is able to bind to RHOA in both the GDP and GTP bound form in vitro, but displays higher affinity for GTP-bound RHOA (Habas et al, 2001; Liu et al, 2007). Studies in Xenopus have identified a DVL-associated weak guanine exchange factor (WGEF) that promotes the exchange of GDP for GTP on RHOA and is required for WNT-PCP signaling (Tanegashima et al, 2008). Evidence suggests that a similar GEF activity is associated with the DVL-DAAM1-RHOA complex in human cells, but the protein has not been definitively identified (Habas et al, 2001; Liu et al, 2007). GTP-bound RHOA relieves the auto-inhibition of RHO-associated kinases, allowing them to dimerize and effect changes to cytoskeletal organization (reviewed in Amano et al, 2010; Lai et al, 2009). DAAM1 may also play a more direct role in regulating the cytoskeleton in response to WNT signaling, since FH domains have been shown to bind actin directly to nucleate linear actin cables (Sagot et al, 2002; Watanabe and Higashida, 2004).

Literature References

PubMed ID	Title	Journal	Year
19365405	Wnt/Fz signaling and the cytoskeleton: potential roles in tumorigenesis Chien, AJ, Lai, SL, Moon, RT	Cell Res.	2009
15501440	Formins: processive cappers of growing actin filaments Higashida, C, Watanabe, N	Exp. Cell Res.	2004
11779461	Wnt/Frizzled activation of Rho regulates vertebrate gastrulation and requires a novel Formin homology protein Daam1 Kato, Y, He, X, Habas, R	Cell	2001
18256687	WGEF activates Rho in the Wnt-PCP pathway and controls convergent extension in Xenopus gastrulation Zhao, H, Dawid, IB, Tanegashima, K	EMBO J.	2008
18162551	Mechanism of activation of the Formin protein Daam1 Runnels, LW, Bharti, R, Khadka, D, Sato, A, Diaz, H, Habas, R, Liu, W	Proc Natl Acad Sci U S A	2008
12134165	An actin nucleation mechanism mediated by Bni1 and profilin Sagot, I, Moseley, J, Rodal, AA, Goode, BL, Pellman, D	Nat. Cell Biol.	2002
20803696	Rho-kinase/ROCK: A key regulator of the cytoskeleton and cell polarity Kaibuchi, K, Nakayama, M, Amano, M	Cytoskeleton (Hoboken)	2010