RAC2

Rac2 is a member of the Rho family of small GTPases, a class of molecular switches that regulate a wide range of intracellular signaling pathways. The RAC2 protein is encoded by the RAC2 gene in humans and is expressed predominantly in hematopoietic cells, including neutrophils, lymphocytes, and monocytes. It plays a central role in reorganizing the actin cytoskeleton, which in turn influences cell shape, adhesion, and migration—key processes for immune cell trafficking and function.

As a small GTPase, RAC2 cycles between an active GTP-bound state and an inactive GDP-bound state. Activation is mediated by guanine nucleotide exchange factors (GEFs) that promote GDP release, while GTP hydrolysis is accelerated by GTPase-activating proteins (GAPs). In its active form, RAC2 interacts with downstream effectors such as p21-activated kinases (PAKs) and the WAVE/SCAR complex to drive actin polymerization and membrane remodeling. In phagocytes, RAC2 also contributes to the assembly and activity of the NADPH oxidase complex, supporting the respiratory burst used to kill ingested microbes.

RAC2 is essential for several immune cell responses. In neutrophils and other phagocytes, it governs chemotaxis, degranulation, and phagocytosis, and it influences vesicular trafficking and integrin signaling. Its activity is spatially and temporally regulated to ensure effective immune responses while preventing inappropriate activation.

Clinical and research significance: Loss-of-function mutations in RAC2 have been associated with immunodeficiency, including impaired T and B cell function. Alterations in RAC2 signaling have been explored in hematologic malignancies and inflammatory diseases. Mouse and cellular models continue to clarify RAC2-specific contributions that are distinct from the closely related RAC1 protein.

RAC2 remains a key mediator of immune cell signaling and cytoskeletal dynamics, with ongoing research exploring its potential as a therapeutic target in immune-related disorders.