rac, a novel ras-related family of proteins that are botulinum toxin substrates

Didsbury, John; Weber, Richard F.; Bokoch, Gary M.; Evans, Tony; Snyderman, Ralph

doi:10.1016/s0021-9258(19)84716-6

Cited by 521 publications

(66 citation statements)

References 52 publications

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“…Ras GTPases could be activated by various growth factor receptors and adhesion receptors in the plasma membrane, thus promoting the signal transduction of key signaling pathways, including extracellular‐regulated kinase (ERK), mitogen‐activated protein kinase, and phosphatidylinositol 3‐kinase . These signaling pathways play important roles in cell secretion, polarization, morphological changes of neurons and axons, and axonogenesis . There is evidence showing that the expression of Rac1 and Rac2 is required for prune spurious axons and branches .…”

Section: Resultsmentioning

confidence: 99%

“…27 These signaling pathways play important roles in cell secretion, polarization, morphological changes of neurons and axons, and axonogenesis. [27][28][29] There is evidence showing that the expression of Rac1 and Rac2 is required for prune spurious axons and branches. 30 Overexpression of them inhibited neurite outgrowth and induced axonal untimely death, while the suppression or loss-of-function of Racs enhanced ectopic axons and branches, and cell survival.…”

Section: Discussionmentioning

confidence: 99%

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Identification of gene coexpression modules, hub genes, and pathways related to spinal cord injury using integrated bioinformatics methods

Wang

Zhang

et al. 2019

J of Cellular Biochemistry

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Spinal cord injury (SCI) is characterized by dramatic neurons loss and axonal regeneration suppression. The underlying mechanism associated with SCI‐induced immune suppression is still unclear. Weighted gene coexpression network analysis (WGCNA) is now widely applied for the identification of the coexpressed modules, hub genes, and pathways associated with clinic traits of diseases. We performed this study to identify hub genes associated with SCI development. Gene Expression Omnibus (GEO) data sets GSE45006 and GSE20907 were downloaded and the significant correlativity and connectivity between them were detected using WGCNA. Three significant consensus modules, including 567 eigengenes, were identified from the master GSE45006 data following the preconditions of approximate scale‐free topology for WGCNA. Further bioinformatics analysis showed these eigengenes were involved in inflammatory and immune responses in SCI. Three hub genes Rac2, Itgb2, and Tyrobp and one pathway “natural killer cell‐mediated cytotoxicity” were identified following short time‐series expression miner, protein‐protein interaction network, and functional enrichment analysis. Gradually upregulated expression patterns of Rac2, Itgb2, and Tyrobp genes at 0, 3, 7, and 14 days after SCI were confirmed based on GSE45006 and GSE20907 data set. Finally, we found that Rac2, Itgb2, and Tyrobp genes might take crucial roles in SCI development through the “natural killer cell–mediated cytotoxicity” pathway.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identification of gene coexpression modules, hub genes, and pathways related to spinal cord injury using integrated bioinformatics methods

Wang

Zhang

et al. 2019

J of Cellular Biochemistry

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“…Since Rac is known to be involved in the formation of lamellipodia (Etienne-Manneville & Hall, 2002;Kölsch et al, 2008;Ridley et al, 1992) and cell adhesion structures (Sugihara et al, 1998;Yap & Kovacs, 2003) and we have shown that BK is involved in the induction of these processes, we also investigated Rac expression. Of the three isoforms described, only the Rac1 isoform was studied since it is the only one that is expressed in all cell types (Didsbury, Weber, Bokoch, Evans, & Snyderman, 1989;Haataja, Groffen, & Heisterkamp, 1997). It has been reported that during cell migration, Rac1, through Arp2/3, mediates the assembly of actin branching filaments at the leading edge (Ridley, 2003;Ridley et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

Bradykinin mediates the association of collecting duct cells to form migratory colonies, through B2 receptor activation

Guaytima

Brandán

Favale

et al. 2018

Journal Cellular Physiology

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It is known that bradykinin (BK) B2 receptor (B2R) is expressed in the collecting duct (CD) cells of the newborn rat kidney, but little is known about its role during early postnatal life. Therefore, we hypothesize that BK could participate in the mechanisms that mediate CD formation during the postnatal renal development. Performing primary cultures, combined with biochemical, immunocytochemical, and time-lapse analysis, we studied the role of BK in CD cell behavior isolated from renal papilla of neonatal rats. A reverse relationship was observed between B2R expression and the degree of CD epithelial cell sheet maturation. BK stimulation induced CD cell association upon B2R activation. The lack of B2R expression in cells showing mature adherens junctions suggested that BK is mostly involved in early adhesive events, thus favoring the initial formation of CD during development. Time-lapse analysis revealed that BK induced a high protrusive activity of CD cells, denoted by ruffle formation and lamellipodia extension. PI3K was involved in the BK-induced CD cell-cell association and the acquisition of the migratory phenotype since, when inhibited, membrane ruffles, and filopodia between cells diminished. Results indicate that the actions of BK mediated by PI3K activation were due to the downstream Akt and Rac pathways. This study, performed with CD cells that were not genetically manipulated, provides new experimental evidence supporting a novel role of BK in rat renal CD organization. As B2R blockade results in abnormal tubular differentiation, our results contribute to better understanding the etiology of human congenital renal malformation and diseases.

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“…The protein encoded turned out to share 35% homology with H-Ras [25]. Subsequently, the group of Snyderman identified Rac1 and Rac2 in 1989 [26]. The third member of Rho family CDC42 was first identified in yeast as S.cerevisiae cell division-cycle 42 and subsequently by Polakis in 1989 [27].…”

Section: The Rho Gtpasesmentioning

confidence: 99%

“…Human Cdc42 shows 80% amino acid identity with yeast CDC42, 50% and 70% respectively with mammalian RhoA and Rac1 proteins [26]. Till date, 20 members of the Rho subfamily have been identified in mammals including the well studied RhoA, Rac1 and Cdc42 (Figure 3).…”

Section: The Rho Gtpasesmentioning

confidence: 99%

Interaction of RhoD and ZIP kinase modulates actin filament assembly and focal adhesion dynamics

Nehru

Almeida

Aspenström

2013

Biochemical and Biophysical Research Communications

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rac, a novel ras-related family of proteins that are botulinum toxin substrates

Cited by 521 publications

References 52 publications

Identification of gene coexpression modules, hub genes, and pathways related to spinal cord injury using integrated bioinformatics methods

Identification of gene coexpression modules, hub genes, and pathways related to spinal cord injury using integrated bioinformatics methods

Bradykinin mediates the association of collecting duct cells to form migratory colonies, through B2 receptor activation

Interaction of RhoD and ZIP kinase modulates actin filament assembly and focal adhesion dynamics

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