Rho protein

C. botulinum C3-toxin and related toxins Rho proteins ADP-ribosylation Inhibition of RhoA, B,C Destruction of the cytoskeleton... 

Bordetella DNT Rho proteins Transglutamination Activation of RhoA, Rac, Cdc42... 

The ETa receptor activates G proteins of the Gq/n and G12/i3 family. The ETB receptor stimulates G proteins of the G and Gq/11 family. In endothelial cells, activation of the ETB receptor stimulates the release of NO and prostacyclin (PGI2) via pertussis toxin-sensitive G proteins. In smooth muscle cells, the activation of ETA receptors leads to an increase of intracellular calcium via pertussis toxin-insensitive G proteins of the Gq/11 family and to an activation of Rho proteins most likely via G proteins of the Gi2/i3 family. Increase of intracellular calcium results in a calmodulin-dependent activation of the myosin light chain kinase (MLCK, Fig. 2). MLCK phosphorylates the 20 kDa myosin light chain (MLC-20), which then stimulates actin-myosin interaction of vascular smooth muscle cells resulting in vasoconstriction. Since activated Rho... 

A subfamily of Rho proteins, the Rnd family of small GTPases, are always GTP-bound and seem to be regulated by expression and localization rather than by nucleotide exchange and hydrolysis. Many Rho GTPase effectors have been identified, including protein and lipid kinases, phospholipase D and numerous adaptor proteins. One of the best characterized effector of RhoA is Rho kinase, which phosphorylates and inactivates myosin phosphatase thereby RhoA causes activation of actomyosin complexes. Rho proteins are preferred targets of bacterial protein toxins ( bacterial toxins). 

C. difficile history of antibiotic use, advanced age, underlying illness 5-10 days of antibacteria treatment (range 1st day to 10 weeks of antibiotics) mild to severe inflammatory diarrhea toxins A and B monoglucosylation of Rho protein - disruption of actin cytoskeleton —> mucosal disruption. - COX-2 - prostaglandin E2 —> synthesis of inflammatory cytokines... 

Just I, Wilm M, Selzer J, Rex G, von Eichel-Streiber C, Mann M, Aktories K The enterotoxin from Clostridium difficile (ToxA) mono-glucosylates the Rho proteins. J Biol Chem 1995 270 13932-13936. 

Antibiotics alter the normal colonic flora, leading to loss of colonization resistance, which is the ability of the normal flora to protect against overgrowth of pathogens, especially when the anaerobic flora are depleted [15], In CDAD, the altered colonization resistance can allow for the overgrowth of C. difficile in the colon. The bacteria produces two toxins which cause disease (toxin A, an enterotoxin, and toxin B, a cytotoxin). The toxins of C. difficile inactivate Rho proteins, which results in the loss of cytoskeletal integrity in enterocytes. Cellular damage results in fluid loss, exudation and diarrhea. The most severe form of C. difficile diarrhea is pseudomembranous colitis, which can cause severe colitis, toxic colon and rarely colon perforation and death. 

The Ras and Rho proteins are involved in signal transduction Ran, Rab and Arf proteins regulate events of the intracellular transport. The function of Rad-proteins is not yet clear. 

A functional connection between the Rho proteins has been observed. Cdc42 may lead to the activation of Rac which for its part can activate Rho [126]. The... 

However, 2 also affected the regulation of actin stress fiber formation [19]. Rho proteins are involved in the regulation of various cytoskeletal structures, and RhoB is believed to be one of the prime targets of FTase inhibitors. Rho B is apparently both geranylgeranylated and farnesylated [20, 21]. If cells were treated with 2, vesicular localization of Rho B was inhibited. Thus 2 may also inhibit the farnesylation of Rho B, thereby interfering with actin stress fiber formation [22]. 

LPA binds and activates specific G-protein-coupled receptors found in many cells (review Moolenaar et al., 1997). The LPA receptor can transmit the signal to G,-, Gj-or Gi2-proteins. If Gq is involved, an InsPs and Ca signal is produced in the cell, whereas signal conduction via Gi- or Gu-proteins flows into the Ras pathway or activates the Rho proteins, respectively (see Chapter 9). 

Denhardt DT. Signal-transducing protein phosphorylation cascades mediated by Ras/Rho proteins in the mammalian cell the potential for multiplex signalling. B/oc/jeraJ 1996 318 729-747. 

Rho and other termination factors. Termination proteins can also react with specific regions of DNA or of an RNA transcript to terminate transcription.183 The best known termination factor is the rho protein a hexamer of 45-kDa subunits. It interacts with transcripts at specific termination sequences, which are often C-rich, and in a process accompanied by hydrolysis of ATP causes release of both RNA and the polymerase from the DNA.192193 Additional E. coli proteins, products of genes nus A and nus G, cooperate with the rho factor at some termination sequences.194-196c The rho hexamer is a helicase that moves along the RNA transcript in the 5 —> 3 direction driven by ATP hydrolysis. If it locates an appropriate termination signal, it may utilize its helicase activity to uncoil the DNA-RNA hybrid segment within the transcription bubble (Fig. 28-4).197 198b... 

Bear, D. G., and D. W. Peabody, The E. coli rho protein An ATPase that terminates transcription. Trends Biochem. Sci. 13 343-348, 1988. 

The discovery of DRhoGEF2 and demonstration of its requirement for gastrulation during early morphogenesis in Drosophila provided early evidence for a direct linkage between the heterotrimeric G proteins and regulation of Rho proteins (Cta and Rhol in Drosophila, respectively) (Barrett et al., 1997 Hacker and Perrimon, 1998). In these studies,... 

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