Identifiers
HUGO:DIAPH1
diaphanous homolog 1 (Drosophila)
HUGO:DIAPH1, HGNC:2876, ENTREZ:1729, GENECARDS:GC05M140875, UNIPROT:O60610
Maps_Modules
HMC:AVOIDING_IMMUNE_DESTRUCTION
Adaptive Immune Response / TCR_SIGNALING
HMC:ACTIVATING_INVASION_AND_METASTASIS
EMT Senescence / EMT_REGULATORS
EMT Senescence / CYTOSKELETON_POLARITY
References
PMID:17306570
PMID:15866170
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.
PMID:16292343
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
PMID:17575049
Positive feedback between Dia1, LARG, and RhoA regulates cell morphology and invasion.
References
em_emtc_emtc_re702( EMT Senescence ):
PMID:17575049
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.