The Hematopoiesis-Specific GTP-Binding Protein RhoH Is GTPase Deficient and Modulates Activities of Other Rho GTPases by an Inhibitory Function

RhoH activity is modulated by interaction with other Rho GTPases, transcriptional regulation, or phosphorylation rather than through classical GTPase cycling and effector modulation.

“Its activity is modulated by interaction with other Rho GTPases [19,20], transcriptional regulation [19] or phosphorylation [21] rather than through the classical cycling process and modulation by effector proteins.”

In a nucleotide dissociation assay, RhoH binds GTP rapidly but does not hydrolyse bound GTP to GDP.

“In a nucleotide dissociation assay it was shown that although RhoH is able to bind GTP rapidly, it does not hydrolyse the bound GTP to GDP [19].”

PMA reduces endogenous RhoH transcripts in Jurkat cells after 60-80 min by 80% of baseline, while TNFα treatment does not regulate RhoH mRNA levels.

“Li et al. tested a couple of stimuli on Jurkat cells and reported that PMA reduces endogenous RhoH transcripts after 60–80 min by 80% of the baseline level, while TNFα treatment did not act as a regulator of RhoH mRNA levels [19].”

High RhoH amounts suppress IKKβ expression necessary for NFκB activation.

“Initial experiments showed that IKKβ expression that is necessary for NFκB activation is suppressed in the presence of high RhoH amounts, presumably because RhoH inhibits IκB degradation.”

RhoH overexpression does not induce activation of p38, JNK or Erk itself, but acts as a specific negative regulator for Rac- and RhoA-induced p38 activity.

“Again, as with NFκB, RhoH overexpression did not induce activation of any of these proteins itself, but rather acted as a specific negative regulator for Rac and RhoA-induced p38 activity.”

RhoH reduces RhoA-, Rac1- or Cdc42-induced activation of the transcription factor NFκB.

“RhoH was shown to reduce the RhoA, Rac1 or Cdc42-induced activation of the transcription factor NFκB.”

RhoH is diffusely distributed in the cytoplasm, and RhoH overexpression causes no difference in morphology of PDGF-stimulated cells.

“The authors describe RhoH to be diffusely distributed in the cytoplasm and they saw no difference in the morphology of PDGF stimulated cells in the presence or absence of RhoH overexpression [19].”

In Jurkat cells stimulated with TNFα, RhoH decreases NFκB activity.

“Jurkat cells stimulated with TNFα show decreased NFκB activity in the presence of RhoH [19].”

RhoH is GTPase-deficient.

“Since RhoH is GTPase-deficient, other mechanisms must be available to regulate the activity or function of the protein, one being the possibility of transcriptional regulation.”

The level of RhoH is approximately 3 times higher in the Th1 subset than in the Th2 subset.

“Indeed, the level of RhoH is app. 3 times higher in the Th1 subset.”

RhoGAP p50 does not enable RhoH to hydrolyse GTP.

“The authors investigated whether the RhoGAP p50 which acts as a GAP for RhoA, Rac and Cdc42 might enable RhoH to hydrolyse GTP, but found it not the case.”

RhoH is an atypical Rho GTPase that is constitutively active and not regulated by classical GTP/GDP cycling.

“The haematopoietic GTPase RhoH is an atypical family member of the Rho GTPases as it is constitutively active and not regulated through the classical cycling between GTP- and GDP-bound state.”

Re-stimulation of cells on day 3 using anti-CD3 leads to a decrease of RhoH expression in Th1 cells, whereas no obvious changes occur in Th2 cells.

“Re-stimulation of cells on day 3 using anti-CD3 led to a decrease of RhoH expression in Th1 cells whereas no obvious changes seemed to have occurred in the Th2 cells.”