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 Regulation of RAC1 activity

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G-protein signaling Regulation of RAC1 activity

Regulation of Rac1 activation

Ras-related C3 botulinum toxin substrate 1 ( Rac1 ) belongs to the Rho subgroupof a family of small GTP-binding proteins (G-proteins) called monomeric G-proteins.Proteins belonging to the Rho subgroup are involved in cytoskeletal control, regulationof the formation of the stress fibers, focal adhesions, cell growth, membranetrafficking, development, and axon guidance and extension [1].

Rac1 is a target of posttranslational modification via attachment of lipidmoieties, such as geranyl, catalyzed by Geranylgeranyltransferase type I ( GGTF-I). These posttranslational modifications affect localization and biological activity ofRac1 [2].

Like other G-proteins, Rac1 is found in two interconvertible forms, GDP-boundinactive and GTP-bound active forms.

Conversion from GTP-bound form (active G-protein) to GDP-bound form (inactiveG-protein) is a result of intrinsic GTPase activity of Rac1. This activity isslow, and proteins called GTPase activated proteins (GAPs), such as Rho GTPase activatingprotein 1 ( RhoGAP1 ), Rac GTPase activating protein 1 ( RacGAP1 ), RICSRho GTPase-activating protein ( p200RhoGAP ), Rho GTPase activating protein 9 (ARHGAP9 ), Active BCR-related gene ( ABR ), Breakpoint cluster region (BCR ), Chimerin 2 ( B-chimaerin ), and RalA binding protein 1 (RalBP1 ), are known to stimulate it, thereby inactivating G-proteins.

Rho-family proteins are found in the cytosol in the GDP-bound inactive formcomplexed with GTPase dissociation inhibitors (GDIs), such as Rho GDP dissociationinhibitor alpha and beta ( RhoGDI alpha and LyGDI ). The GDP-bound form isfirst released from the GDI via a hitherto unknown mechanism and is converted to theGTP-bound by the Guanine nucleotide exchange factors (GEFs). GEFs activate G-proteins[1].

The several GEFs are known to interact with Rac1. These are Vav 1 and 2 GEFs (VAV-1 and VAV-2 ), MCF.2 cell line derived transforming sequence (DBL ), T-cell lymphoma invasion and metastasis 1 ( Tiam1 ), Epithelial celltransforming sequence 2 oncogene ( ECT2 ), Rho/Rac GEF 2 ( ARHGEF2 ) andothers.

The activity of GAPs, GEFs and GDIs is regulated by multiple intracellular processes,but precise pathways involved in these are not apparent.

The most extensively studied GEFs for Rac1 are VAV proteins. VAV-2 isrecruited by the CD19 co-receptor of the B cells and participates in the B cellreceptor signaling [3]. In the T cell, VAV-1 forms complex withLymphocyte cytosolic protein 2 ( Slp76 ) linker protein. Complex VAV-1/Slp76 is involved in the T cell receptor ( TCR alpha/beta ) and CD28signaling cascades [4].

Small GTPase pathways can cross-talk. E.g., v-Ha-ras Harvey rat sarcoma viral oncogenehomolog ( H-Ras ) activates Tiam 1, an exchange factor for Rac1.That leads to Rac1 activation. On the other hand, RalBP1, an effector forv-Ral simian leukemia viral oncogene homolog A and B (RalA and RalB), inactivatesRac1 [5], [6].