Reactome | RAC1 GTPase cycle

RAC1 GTPase cycle

Stable Identifier

R-HSA-9013149

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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This pathway catalogues RAC1 guanine nucleotide exchange factors (GEFs), GTPase activator proteins (GAPs), GDP dissociation inhibitors (GDIs) and RAC1 effectors (reviewed by Payapilli and Malliri 2018). RAC1 is one of the three best characterized RHO GTPases, the other two being RHOA and CDC42. RAC1 regulates the cytoskeleton and the production of reactive oxygen species (ROS) (Acevedo and Gonzalez-Billault 2018) and is involved in cell adhesion and cell migration (Marei and Malliri 2017). RAC1 is involved in neuronal development (de Curtis et al. 2014). In neurons, RAC1 activity is regulated by synaptic activation and RAC1-mediated changes in actin cytoskeleton are implicated in dendritic spine morphogenesis, which plays a role in memory formation and learning (Tajeda-Simon 2015; Costa et al. 2020). RAC1 is involved in metabolic regulation of pancreatic islet β-cells and in diabetes pathophysiology (Kowluru 2017; Kowluru et al. 2020). RAC1-mediated activation of NOX2 contributes to mitochondrial damage and the development of retinopathy in patients with diabetes (Sahajpal et al. 2019). RAC1 is important for exercise and contraction-stimulated glucose uptake in skeletal muscles (Sylow et al. 2014). RAC1 plays an important role in the maintenance of intestinal barrier integrity under physiological conditions and during tissue repair after resolution of colitis. Toxins of many diarrhea-causing bacteria target RAC1 (Kotelevets and Chastre 2020). RAC1 is important for skin homeostasis and wound healing and is involved in the pathogenesis of psoriasis (Winge and Marinkovich 2019). RAC1 is essential to vascular homeostasis and chronically elevated RAC1 signaling contributes to vascular pathology (Marinkovic et al. 2015). RAC1 hyperactivation, mutation and copy-number gain are frequently observed in solid tumors (Zou et al. 2017; De et al. 2019; De et al. 2020; Cannon et al. 2020; Kotelevets and Chastre 2020).

Literature References

PubMed ID	Title	Journal	Year
27790713	Emerging roles of RAC1 in treating lung cancer patients Zou, T, Mao, X, Yin, J, Li, X, Chen, J, Zhu, T, Li, Q, Zhou, H, Liu, Z	Clin. Genet.	2017
28202288	Tiam1/Vav2-Rac1 axis: A tug-of-war between islet function and dysfunction Kowluru, A	Biochem. Pharmacol.	2017
32460002	RAC1 as a Therapeutic Target in Malignant Melanoma Cannon, AC, Uribe-Alvarez, C, Chernoff, J	Trends Cancer	2020
28055293	Epidermal activation of the small GTPase Rac1 in psoriasis pathogenesis Winge, MCG, Marinkovich, MP	Small GTPases	2019
32362820	The Role of Rac GTPase in Dendritic Spine Morphogenesis and Memory Costa, JF, Dines, M, Lamprecht, R	Front Synaptic Neurosci	2020
29330095	Crosstalk between Rac1-mediated actin regulation and ROS production Acevedo, A, González-Billault, C	Free Radic. Biol. Med.	2018
25239922	Rac1--a novel regulator of contraction-stimulated glucose uptake in skeletal muscle Sylow, L, Møller, LL, Kleinert, M, Richter, EA, Jensen, TE	Exp. Physiol.	2014
25309333	Roles of Rac1 and Rac3 GTPases during the development of cortical and hippocampal GABAergic interneurons de Curtis, I	Front Cell Neurosci	2014
31027363	RAC1 Takes the Lead in Solid Tumors De, P, Aske, JC, Dey, N	Cells	2019
29723737	Compartmentalisation of RAC1 signalling Payapilly, A, Malliri, A	Curr. Opin. Cell Biol.	2018
32545340	Active RAC1 Promotes Tumorigenic Phenotypes and Therapy Resistance in Solid Tumors De, P, Rozeboom, BJ, Aske, JC, Dey, N	Cancers (Basel)	2020
25818528	Modulation of actin dynamics by Rac1 to target cognitive function Tejada-Simon, MV	J. Neurochem.	2015
31277234	The Regulatory Role of Rac1, a Small Molecular Weight GTPase, in the Development of Diabetic Retinopathy Sahajpal, N, Kowluru, A, Kowluru, RA	J Clin Med	2019
32634437	Potential roles of PP2A-Rac1 signaling axis in pancreatic β-cell dysfunction under metabolic stress: Progress and Promise Kowluru, A	Biochem. Pharmacol.	2020
26036474	The Ins and Outs of Small GTPase Rac1 in the Vasculature Marinković, G, Heemskerk, N, Van Buul, JD, de Waard, V	J. Pharmacol. Exp. Ther.	2015
32178475	Rac1 Signaling: From Intestinal Homeostasis to Colorectal Cancer Metastasis Kotelevets, L, Chastre, E	Cancers (Basel)	2020
27314616	GEFs: Dual regulation of Rac1 signaling Marei, H, Malliri, A	Small GTPases	2017