DRFs (DIAPH1,2,3) are autoinhibited through intramolecular binding of a Diaphanous autoinhibitory domain to a conserved N-terminal regulatory element.
Autoinhibition is relieved through binding of the GTPase RhoA to the N-terminal element.
DRFs are regulated by a RhoGTPase-binding domain situated in the N-terminal region and a C-terminal Diaphanous-autoregulatory domain, whose interaction stabilises an autoinhibited inactive conformation.
Binding of active Rho releases DAD and activates the catalytic activity of mDia
Positive feedback between Dia1, LARG, and RhoA regulates cell morphology and invasion.
e_re702( EMT ):
Positive feedback between Dia1 (so-called DIAPH1), LARG (so-called ARHGEF12), and RhoA regulates cell morphology and invasion.
The FH2 domain of Dia1 stimulates the guanine nucleotide exchange activity of LARG in vitro.
Dia1 is necessary for LPA-stimulated Rho-ROCK signaling and bleb-associated cancer cell invasion.
Thus, Dia1-dependent RhoA activation constitutes a positive feedback mechanism to modulate cell behavior.
Dia1 is required and sufficient for full LPA- induced activation of RhoA and downstream ROCK signaling. This effect can be mediated through interaction of Dia1 with LARG
Dia1, in addition to its role as a downstream RhoA effector, can function upstream of RhoA.
In compartment: Cytoplasm
Participates in complexes:
Participates in reactions:
As Reactant or Product:
- DIA*|closed@Cytoplasm → DIAPH1@Cytoplasm
- DIAPH1@Cytoplasm → ARHGEF12@Cytoplasm
- RhoB_cytoskeletal_effectors*@Cytoplasm → DIAPH1@Cytoplasm
- RhoA_cytoskeletal_effectors*@Cytoplasm → DIAPH1@Cytoplasm