Rac Protein
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Rac is a subfamily of the
Rho family of GTPases The Rho family of GTPases is a family of small (~21 kDa) signaling G proteins, and is a subfamily of the Ras superfamily. The members of the Rho GTPase family have been shown to regulate many aspects of intracellular actin dynamics, and are found ...
, small (~21 kDa) signaling
G protein G proteins, also known as guanine nucleotide-binding proteins, are a Protein family, family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell (biology), ...
s (more specifically a
GTPase GTPases are a large family of hydrolase enzymes that bind to the nucleotide guanosine triphosphate (GTP) and hydrolyze it to guanosine diphosphate (GDP). The GTP binding and hydrolysis takes place in the highly conserved P-loop "G domain", a ...
). Just as other G proteins, Rac acts as a molecular switch, remaining inactive while bound to guanosine diphosphate (GDP) and activated once
guanine nucleotide exchange factor Guanine nucleotide exchange factors (GEFs) are proteins or protein domains that activate monomeric GTPases by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP). A variety of unrelated structu ...
s (GEFs) remove GDP, permitting
guanosine triphosphate Guanosine-5'-triphosphate (GTP) is a purine nucleoside triphosphate. It is one of the building blocks needed for the synthesis of RNA during the transcription process. Its structure is similar to that of the guanosine nucleoside, the only di ...
(GTP) to bind. When bound to GTP, Rac is activated. In its activated state, Rac participates in the regulation of cell movement, through its involvement in structural changes to the actin
cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...
. By changing the cytoskeletal dynamics within the cell, Rac-GTPases are able to facilitate the recruitment of neutrophils to the infected tissues, and to regulate degranulation of azurophil and integrin-dependent phagocytosis. Activated Rac also regulates the effector functions of the target proteins involved in downstream signaling. As an essential subunit of NOX2 (NADPH oxidase enzyme complex), Rac is required for ROS (reactive oxygen species) production involved in the formation of NETs (neutrophil extracellular traps, thus, facilitating the pathogen and debris clearance by neutrophils, and the reduction of inflammation. The abnormal activities of Rac including its hyperactivation, resistance to degradation, and abnormal localization of its signaling protein components were found to facilitate the development of cancerous cells and resist to anticancer treatment. Recent experiments on ''Drosophila'' suggest that Rac could be involved in mediating the process of forgetting. Hyperactivation of Rac increases memory decay whereas its inhibition prevents interference-induced forgetting and slows down passive memory decay.


Classification

The Rho family of GTPases includes Rac, Rho, and
Cdc42 Cell division control protein 42 homolog (Cdc42 or CDC42) is a protein that in humans is encoded by the ''CDC42'' gene. Cdc42 is involved in regulation of the cell cycle. It was originally identified in ''S. cerevisiae'' (yeast) as a mediator of ...
small G-protein groups. Rac comprises Rac1,
Rac2 Rac2 (Ras-related C3 botulinum toxin substrate 2) is a small (~21 kDa) signaling G protein (to be specific, a GTPase), and is a member of the Rac subfamily of the family Rho family of GTPases. It is encoded by the gene RAC2. Members of Rho fami ...
, Rac3, and RhoG subgroups. The extensive cross-talk within these groups of GTPase provides a significant impact on the biological responses of the cell, influencing the activity of the cell cycle machinery. Ras cooperates with Cdc42 to regulate Elk1 phosphorylation and transcriptional activity of SRF. Ras also cooperates with Rho and Ras to activate other downstream signaling pathways.


References

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