Map Key
Generic Enzyme
Generic kinase
Protein kinase
Lipid kinase
Generic phosphatase
Protein phosphatase
Lipid phosphatase
Generic phospholipase
Generic protease
RAS - superfamily
G beta/gamma
Regulators (GDI, GAP, GEF)
Generic channel
Ligand-gated channel
Voltage-gated channel
Normal process
Pathological process
Positive effect
Negative effect
Unspecified effect
Technical link
Disrupts in disease
Emerges in disease
Enhances in disease
Weakens in disease
Organsim specific interaction

Generic binding protein
Receptor ligand
Cell membrane glycoprotein
Transcription factor
Inorganic ion
Predicted metabolite or user's structure
Generic receptor
Receptors with enzyme activity

Normal process
Pathological process
Covalent modifications
Transcription regulation
MicroRNA binding
Influence on expression
Unspecified interactions
Pharmacological effect
Toxic effect
Group relation
Complex subunit
Similarity reaction
A complex or a group
Organism specific object

G-protein signaling Rac2 regulation pathway

Log In to Post A Comment

G-protein signaling Rac2 regulation pathway

Rac2 regulation pathway

Ras-related C3 botulinum toxin substrate 2 ( Rac2 ) belongs to family of smallRho guanosine triphosphatases (GTPases) and it is a critical signaling regulator inmammalian cells. Expression of Rac2 is restricted to cells of hematopoieticorigin. It plays critical roles in a wide variety of primary hematopoietic cells,including the regulation of adhesion, migration, oxidase activity, and gene expression[1], [2], [3], [4], [5].

Main transcriptional activators of Rac2 promoter are Sp1 and Sp3 transcriptionfactors ( SP1 and SP3 ) [6]. Activation of Rac proteins ismediated by guanine nucleotide exchange factors (GEFs), main GEFs for Rac2 areT-cell lymphoma invasion and metastasis 1 ( TIAM1 ) [7],Phosphatidylinositol 3,4,5-trisphosphate-dependent RAC exchanger 1 ( PREX1 )[8], [9] and Vav 1 guanine nucleotide exchange factor (VAV-1 ) [10] which is most efficient in inducing oxidase activity ofRac2 [5].

Rac2 is isoprenylated at its C-terminus by Geranylgeranyltransferase type I (GGTase-I ), such modification may influence on Rac2 membrane transport fromcytosol [11], [12].

Rac2 activity is inhibited by GTPase-activating proteins (GAPs), known GAPs forRac2 are Breakpoint cluster region ( BCR ), Active BCR-related gene (ABR ) [13], [14] and Rac GTPase activating protein 1 (RacGAP1 ) [15], [16].

Activated Rac2 interacts with several effectors which promote activation ofimportant cellular pathways. It was shown that Rac2 can bind and activatePhosphoinositide-3-kinase, regulatory subunit 1 ( PI3K reg class IA (p85) ) [17]. Also, Rac2 stimulates Nitric oxide ( NO ) production byinteracting with Nitric oxide synthase 2A ( iNos ) [18], [19]. In addition, Rac2 promotes Phospholipase C, beta 2 ( PLC-beta 2) activation and 1,2-diacyl-glycerol ( DAG ) production [20].

Important effector of Rac2 is p21 protein (Cdc42/Rac)-activated kinase 1 (PAK1 ). Activated by Rac2, it stimulates activity of NADPH oxidasesubunits [21].

NADPH oxidase is a multisubunit complex. It comprises of the Cytochrome b-558,which is a heterodimer composed of a large Cytochrome b-245, beta polypeptide (gp91-phox ) and a small Cytochrome b-245, alpha polypeptide ( p22-phox )subunit. Oxidase activation is controlled by the recruitment of cytosolic regulatoryproteins to the Cytochrome b-558, including the Neutrophil cytosolic factors 1and 2 ( p47-phox and p67-phox ) [5]. Rac2 is a criticalregulator of NADPH oxidase activity and assembly in phagocytic cells [22],[23], [24]. Ezrin ( VIL2(ezrin) ) and Radixin ( RDX(radixin) ) bind to Rho GDP dissociation inhibitor (GDI) alpha ( RhoGDIalpha ) and remove it from binding with Rac2 in cytosol thus promotingRac2 binding to p67-phox and translocation to plasma membrane [25], [26], [27], [28]. Rac2 also binds toNADPH oxidase activator 1 ( NOXA1 ) which stimulates activity of p47-phox[29]. p47-phox and p67-phox bind to Cytochrome b-558subunits and thus promote NADPH oxidase activation, Superoxide anion ( O(2)(-) )production and initiation of oxidative stress [30], [28].