Identification of a novel human Rho protein with unusual properties: GTPase deficiency and in vivo farnesylation

  title={Identification of a novel human Rho protein with unusual properties: GTPase deficiency and in vivo farnesylation},
  author={Rosemary Foster and Kang Quan Hu and Y. Lu and Katherine M Nolan and J. A. Thissen and Jeffrey Settleman},
  journal={Molecular and Cellular Biology},
  pages={2689 - 2699}
We have identified a human Rho protein, RhoE, which has unusual structural and biochemical properties that suggest a novel mechanism of regulation. Within a region that is highly conserved among small GTPases, RhoE contains amino acid differences specifically at three positions that confer oncogenicity to Ras (12, 59, and 61). As predicted by these substitutions, which impair GTP hydrolysis in Ras, RhoE binds GTP but lacks intrinsic GTPase activity and is resistant to Rho-specific GTPase… 
Small GTPases of the Rho family and cell transformation.
  • P. Fort
  • Biology
    Progress in molecular and subcellular biology
  • 1999
The Rho GTPases form a distinct subgroup of the Ras superfamily of low molecular weight GTP binding proteins. These proteins are implicated in signal transduction leading to changes in membrane
Atypical Rho Family Members
Of the 20 Rho GTP-binding proteins in humans, 8 have atypical properties, which are also unusual within the Ras superfamily, and have been implicated in diverse functions, including cell adhesion and migration, vesicle trafficking and cell proliferation.
Rho Family GTPase Modification and Dependence on CAAX Motif-signaled Posttranslational Modification*
A majority of Rho GTPases are targets for pharmacologic inhibitors of farnesyltransferase, Rce1, and Icmt, and the sequence requirements and roles of CAAX signal modifications in dictating the subcellular locations and functions of the RHo GTPase family are determined.
Rho-family GTPases: it's not only Rac and Rho (and I like it)
The Rho-family proteins make up a major branch of the Ras superfamily of small GTPases, and newer members of the family possess additional sequence elements beyond the GTPase domain, which suggests they exhibit yet other mechanisms of regulation.
Identification and characterization of a new isoform of small GTPase RhoE
The identification and characterization of a new isoform of RhoE (RhoEα), a member of the Rho GTPase family, which is generated from the same gene by alternative translation initiation at the downstream ATG codon 46.
Di-Ras, a Distinct Subgroup of Ras Family GTPases with Unique Biochemical Properties*
Interestingly, introduction of Di-Ras into HEK293T cells induces large cellular vacuolation, raising the possibility that Di- Ras might regulate cell morphogenesis in a manner distinct from other members of Ras family.
Insights into the GTP/GDP cycle of RabX3, a novel GTPase from Entamoeba histolytica with tandem G-domains.
It is found that EhRabX3 is extremely sluggish in hydrolyzing GTP, and that could be attributed to its atypical nucleotide binding pocket, and it harbors substitutions at two positions that confer oncogenicity to Ras because of impaired GTP hydrolysis.
Overview of Rho GTPase History
A historical overview of some of the key discoveries that provide the foundation for the current knowledge of Rho GTPase regulation and function is provided, with an emphasis on the importance of deregulated RhoGTPase function in human disease.


Identification of distinct cytoplasmic targets for ras/R-ras and rho regulatory proteins.
Association between GTPase activators for Rho and Ras families
It is shown here that p190 can function as a GAP specifically for members of the rho family, and the formation of a complex between Ras-GAP and p190 in growth-factor stimulated cells may allow the coupling of signalling pathways that involve ras and rho GTPases.
The product of ras is a GTPase and the T24 oncogenic mutant is deficient in this activity
It is reported that the normal ras protein has an intrinsic GTPase activity, yielding GDP and Pi, and it is suggested that this deficiency in GTP enzyme is the probable cause for the transforming phenotype of the T24 protein.
p190 RhoGAP, the major RasGAP-associated protein, binds GTP directly
The sequence of p190 in the GTP-binding domain, which shares structural features with both the Ras-like small GTPases and the larger G proteins, suggests that this protein defines a novel class of guanine nucleotide-binding proteins.
Sequence dependence of protein isoprenylation.
Amino acid 61 is a determinant of sensitivity of rap proteins to the ras GTPase activating protein.
This work has mutated thr61 of p21rap1A to glutamine and shown that ras-GAP is now able to accelerate the rate of hydrolysis of GTP.