Identifiers
Rho guanine nucleotide exchange factor (GEF) 12
HUGO:ARHGEF12, HGNC:14193, ENTREZ:23365, GENECARDS:GC11P120207, UNIPROT:Q9NZN5
Maps_Modules
HMC:ACTIVATING_INVASION_AND_METASTASIS
EMT Senescence / EMT_REGULATORS
EMT Senescence / CYTOSKELETON_POLARITY
References
PMID:11724822
Insulin-like growth factor (IGF)-1 plays crucial roles in growth control and rearrangements of the cytoskeleton
LARG is an Rho guanine nucleotide exchange factor, which contains a PDZ domain responsible for IGF-1 binding.
LARG induced the formation of stress fibers in NIH 3T3 fibroblasts.
MDCKII epithelial cells treated with IGF-1 results in activated Rho and its effector Rho-associated kinase and actin stress fibers were enhanced.
IGF-1 activates the Rho pathway via a LARG/IGF-1 receptor complex and thereby regulates cytoskeletal rearrangements.
PMID:15331592
LARG (so-called ARHGEF12) belongs to a small subfamily of RhoGEFs that are RhoA-selective and directly activated by the G-alpha 12/13 family of heterotrimeric G proteins
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.