Rac is a subfamily of the
Rho family of GTPases,
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 ...
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 GDP and activated once
GEFs 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 comp ...
. 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 2 (Nox2), also known as cytochrome b(558) subunit beta or Cytochrome b-245 heavy chain, is a protein that in humans is encoded by the ''NOX2'' gene (also called ''CYBB'' gene). The protein is a superoxide generating enzyme which for ...
(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 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
G proteins
EC 3.6.5
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