Participation of the small molecular weight GTP-binding protein Rac1 in cell-free activation and assembly of the respiratory burst oxidase. Inhibition by a carboxyl-terminal Rac peptide.

Kreck, M. L.; Uhlinger, David J.; Tyagi, Shiv Raj; Inge, K. L.; Lambeth, J. David

doi:10.1016/s0021-9258(17)41757-1

Cited by 82 publications

(24 citation statements)

References 40 publications

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“…Previous studies have suggested that Rac1 and Rac2 vary in efficiency of interactions with proteins of the NADPH oxidase complex 26,27 and differ in binding affinities with certain effector proteins. 25 In all of these studies, the region spanning the polybasic domain of Rac1 has been implicated.…”

Section: Discussionmentioning

confidence: 99%

“…32,48 Third, superoxide anion production in Rac-dependent cell-free systems has been shown to be inhibited by the Rac1(178-188) peptide that spans the polybasic domain, but not by the corresponding Rac2(178-188) peptide. 26,27 Finally, the TRQQKRP motif of Rac2 and the polybasic domain of Rac1 have been shown to possess different binding affinities and kinase-stimulating activities toward one of the effector proteins, PAK. 25 More recently, Michaelson et al 37 have demonstrated that the sequences upstream of the CAAL motive in Rac1 are sufficient to direct subcellular localization to the plasma membrane and endomembranes in live cells.…”

Section: Discussionmentioning

confidence: 99%

“…25 Moreover, it has been shown that the polybasic domain of Rac1 but not the TRQQKRP motif of Rac2 is important for nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation in cell-free systems. 26,27 The polybasic domain of Rac1 also has been shown to be required for the oligomerization of Rac1. 28 However, it is still not clear to what extent the TRQQKRP motif in Rac2 is critical to the intracellular localization and the functions of this protein.…”

Section: Introductionmentioning

confidence: 99%

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The TRQQKRP motif located near the C-terminus of Rac2 is essential for Rac2 biologic functions and intracellular localization

Wen

Filippi²,

Bailey³

et al. 2002

Blood

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Rac GTPases regulate a wide variety of cellular processes including actin cytoskeleton organization, gene expression, cell-cycle progression, and apoptosis. Here we report that the TRQQKRP motif of Rac2 located near the C-terminus, a region of sequence disparity among Rac proteins, is essential for complementation of Rac2 function in Rac2-deficient cells. Deletion of this sequence can also intragenically suppress the dominant-negative Rac2D57Nmutation in a variety of functional assays. In Rac2-deficient cells, expression of TRQQKRP-deleted Rac2 protein is unable to completely rescue migration and nicotinamide adenine dinucleotide phosphate oxidase deficiencies previously described in these cells. In fibroblasts, the Rac2D57N mutant phenotypes of abnormal proliferation, cell morphology, and membrane ruffling are suppressed by the TRQQKRP motif deletion. In myeloid hematopoietic cells, the deletion of the TRQQKRP motif eliminates a Rac2D57N-induced block in in vitro differentiation of neutrophils not previously described with this mutant. Mechanistically, deletion of the TRQQKRP motif results in diminished geranylgeranylation and delocalization of intracellular Rac2 protein. Taken together, these results indicate that the TRQQKRP motif in Rac2 protein is required for efficient prenylation and correct intracellular localization of Rac2 protein and is essential for Rac2 to mediate a variety of its biologic functions. These data suggest that precise localization of Rac2 protein in intracellular compartments and/or with other proteins/lipids is a prerequisite for its diverse functions.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The TRQQKRP motif located near the C-terminus of Rac2 is essential for Rac2 biologic functions and intracellular localization

Wen

Filippi²,

Bailey³

et al. 2002

Blood

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show abstract

“…Interestingly, none of these residues are included in the "effector loop" (residues 22-45 of Rac). Instead, they are contained in three distinct regions that have been implicated together with the classical effector loop in the recognition of downstream effectors (Kreck et al, 1994;Joseph and Pick, 1995;Diekmann et al, 1995;Westwick et al, 1997). One of the three regions corresponds to a stretch of amino acid residues at the COOH terminus of the polypeptides, which is important also for targeting of the GTPases to the membrane; 6 of the 12 amino acid differences between cRac1A and cRac1B are clustered in this region.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of a Neural-specific Rho Family GTPase, cRac1B, Selectively Induces Enhanced Neuritogenesis and Neurite Branching in Primary Neurons

Albertinazzi

Gilardelli

Paris

et al. 1998

The Journal of Cell Biology

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Rho family GTPases have been implicated in cytoskeletal reorganization during neuritogenesis. We have recently identified a new gene of this family, cRac1B, specifically expressed in the chicken developing nervous system. This GTPase was overexpressed in primary neurons to study the role of cRac1B in the development of the neuronal phenotype. Overexpression of cRac1B induced an increment in the number of neurites per neuron, and dramatically increased neurite branching, whereas overexpression of the highly related and ubiquitous cRac1A GTPase did not evidently affect neuronal morphology. Furthermore, expression of an inactive form of cRac1B strikingly inhibited neurite formation. The specificity of cRac1B action observed in neurons was not observed in fibroblasts, where both GTPases produced similar effects on cell morphology and actin organization, indicating the existence of a cell type-dependent specificity of cRac1B function. Molecular dissection of cRac1B function by analysis of the effects of chimeric cRac1A/cRac1B proteins showed that the COOH-terminal portion of cRac1B is essential to induce increased neuritogenesis and neurite branching. Considering the distinctive regulation of cRac1B expression during neural development, our data strongly support an important role of cRac1B during neuritogenesis, and they uncover new mechanisms underlying the functional specificity of distinct Rho family GTPases.

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“…We have previously developed a "semi-recombinant" cellfree system consisting of isolated plasma membranes as a source of the cytochrome along with purified recombinant p47-phox, p67-phox, and Racl (Uhlinger et al, 1992;Kreck et al, 1994). Herein, we investigated the effect of RGVHFIF on cell-free translocation of p47-phox and on the steadystate kinetics when cytosolic factors are varied.…”

mentioning

confidence: 99%

On the Mechanism of Inhibition of the Neutrophil Respiratory Burst Oxidase by a Peptide from the C-Terminus of the Large Subunit of Cytochrome b558

Tyagi²,

Jd³

1995

Biochemistry

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A peptide (RGVHFIF) from near the carboxyl terminus (residues 559-565) of gp91-phox, the large subunit of cytochrome b558, was previously shown to inhibit activation of the respiratory burst oxidase [Kleinberg, M. E., Malech, H. L., & Rotrosen, D. (1990) J. Biol. Chem. 265, 15577-15583]. The peptide has been proposed to compete with gp91-phox binding to p47-phox, one of the cytosolic oxidase components. In the present studies, we have used a semirecombinant system consisting of recombinant cytosolic factors (p47-phox, p67-phox, and Rac1) along with isolated plasma membrane to investigate the mechanism by which the peptide inhibits oxidase activation. In an in vitro translocation model, the peptide inhibited arachidonate-activated translocation of both p47-phox and p67-phox to the plasma membrane. The kinetic mechanism of inhibition was examined. Inhibition was noncompetitive or mixed with respect to not only Rac and p67-phox but also to p47-phox. We suggest that the peptide, rather than competing for cytochrome-p47-phox interactions, inhibits indirectly, perhaps by binding to and altering the conformation of cytochrome b558.

show abstract

Participation of the small molecular weight GTP-binding protein Rac1 in cell-free activation and assembly of the respiratory burst oxidase. Inhibition by a carboxyl-terminal Rac peptide.

Cited by 82 publications

References 40 publications

The TRQQKRP motif located near the C-terminus of Rac2 is essential for Rac2 biologic functions and intracellular localization

The TRQQKRP motif located near the C-terminus of Rac2 is essential for Rac2 biologic functions and intracellular localization

Overexpression of a Neural-specific Rho Family GTPase, cRac1B, Selectively Induces Enhanced Neuritogenesis and Neurite Branching in Primary Neurons

On the Mechanism of Inhibition of the Neutrophil Respiratory Burst Oxidase by a Peptide from the C-Terminus of the Large Subunit of Cytochrome b558

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