Rac (GTPase)
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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 foun ...
, small (~21 kDa) signaling
G protein G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell to its interior. Their act ...
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 pro ...
). Just as other G proteins, Rac acts as a molecular switch, remaining inactive while bound to GDP and activated once
GEFs Generalized epilepsy with febrile seizures plus (GEFS+) is a syndromic autosomal dominant disorder where affected individuals can exhibit numerous epilepsy phenotypes. GEFS+ can persist beyond early childhood (i.e., 6 years of age). GEFS+ is ...
remove GDP, permitting 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 suggested that Rac could be involved in mediating the process of forgetting. Hyperactivation of Rac increases the memory decay whereas its inhibition prevents interference-induced forgetting and slows down a passive memory decay.


Classification

The Rho family of GTPases includes Rac, Rho, and Cdc42 small G-protein groups. Rac comprises Rac1, Rac2, Rac3, and
RhoG RhoG (Ras homology Growth-related) (or ARGH) is a small (~21 kDa) monomeric GTP-binding protein (G protein), and is an important component of many intracellular signalling pathways. It is a member of the Rac subfamily of the Rho family of small ...
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 Ras or RAS may refer to: Arts and media * RAS Records Real Authentic Sound, a reggae record label * Rundfunk Anstalt Südtirol, a south Tyrolese public broadcasting service * Rás 1, an Icelandic radio station * Rás 2, an Icelandic radio stati ...
to activate other downstream signaling pathways.


References

G proteins EC 3.6.5 {{biochemistry-stub