DAAM1 recruits GTP-bound RHOA

Stable Identifier
Homo sapiens
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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).

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Orthologous Events