Leukemia‐associated Rho guanine nucleotide exchange factor (LARG) links heterotrimeric G proteins of the G12 family to Rho

@article{Fukuhara2000LeukemiaassociatedRG,
  title={Leukemia‐associated Rho guanine nucleotide exchange factor (LARG) links heterotrimeric G proteins of the G12 family to Rho},
  author={Shigetomo Fukuhara and Hiroki Chikumi and J. Silvio Gutkind},
  journal={FEBS Letters},
  year={2000},
  volume={485}
}
A putative guanine nucleotide exchange factor (GEF), termed leukemia‐associated RhoGEF (LARG), was recently identified upon fusion to the coding sequence of the MLL gene in acute myeloid leukemia. Although the function of LARG is still unknown, it exhibits a number of structural domains suggestive of a role in signal transduction, including a PDZ domain, a LH/RGS domain, and a Dbl homology/pleckstrin homology domain. Here, we show that LARG can activate Rho in vivo. Furthermore, we present… 
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Leukemia-Associated Rho Guanine Nucleotide Exchange Factor Promotes Gαq-Coupled Activation of RhoA
TLDR
These findings suggest that the RhoA exchange factor LARG, unlike the related p115 Rho GEF and PDZ-RhoGEF proteins, can serve as an effector for Gq-coupled receptors, mediating their functional linkage to RHoA-dependent signaling pathways.
Regulation of G Protein-linked Guanine Nucleotide Exchange Factors for Rho, PDZ-RhoGEF, and LARG by Tyrosine Phosphorylation
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Evidence is found that the activation of thrombin receptors endogenously expressed in HEK-293T cells leads to a remarkable increase in the levels of GTP-bound Rho within 1 min and a more limited but sustained activation thereafter, which lasts even for several hours.
Leukemia-associated Rho Guanine Nucleotide Exchange Factor, a Dbl Family Protein Found Mutated in Leukemia, Causes Transformation by Activation of RhoA*
TLDR
It is concluded that LARG is a RhoA-specific guanine nucleotide exchange factor and is the first functional Dbl protein mutated in cancer and indicate LARG-mediated activation of RHoA may play a role in the development of human leukemias.
Plexin B Regulates Rho through the Guanine Nucleotide Exchange Factors Leukemia-associated Rho GEF (LARG) and PDZ-RhoGEF*
TLDR
The association of Plexins with LARG and PDZ-RhoGEF thus provides a direct molecular mechanism by which semaphorins acting on Plexin B can control Rho, thereby regulating the actin-cytoskeleton during axonal guidance and cell migration.
Modular architecture and novel protein-protein interactions regulating the RGS-containing Rho guanine nucleotide exchange factors.
TLDR
The experimental strategies that have been utilized to begin unraveling the molecular mechanisms regulating the functional activity of RGS-containing RhoGEFs are described.
Characterization of leukemia-associated Rho guanine nucleotide exchange factor (LARG) expression during murine development
TLDR
Colocalization of the LARG protein with the insulin-like growth factor-I (IGF-1) receptor is demonstrated, suggesting a potential physiologic role for LARG as an activator of RhoA in response to IGF-1.
Dbl family guanine nucleotide exchange factors.
  • Y. Zheng
  • Biology, Medicine
    Trends in biochemical sciences
  • 2001
The Dbl family of guanine nucleotide exchange factors are multifunctional molecules that transduce diverse intracellular signals leading to the activation of Rho GTPases. The tandem Dbl-homology and…
Small-molecule inhibitors targeting G-protein–coupled Rho guanine nucleotide exchange factors
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Studies show that Rho GEFs can serve as selective targets of small chemicals and present a strategy of dual inhibition of the enzyme–substrate pair of GEF–RhoA at their binding interface that leads to enhanced efficacy and specificity.
The Molecular Basis of RhoA Specificity in the Guanine Nucleotide Exchange Factor PDZ-RhoGEF*
TLDR
This work conducts extensive mutational and functional studies of the molecular basis of the RhoA selectivity in PDZ-RhoGEF and finds that selectivity for RHoA versus Cdc42 is defined by a small number of interactions.
Regulation of Rho guanine nucleotide exchange factors by G proteins.
TLDR
The regulation provided by this family of guanine nucleotide exchange factors for Rho proteins is defined by their selective regulation by specific G proteins, phosphorylation by kinases, and potential localization with signaling partners.
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