Disease relevance of Vav2

• We report that this is the case for Vav2, because the disruption of its locus in mice causes tachycardia, hypertension, and defects in the heart, arterial walls, and kidneys [1].

High impact information on Vav2

• These findings establish a role for Vav-2 in BCR calcium signaling and reveal that the Vav family of GEFs is critical to B cell development and function [2].
• Vav-1 and Vav-2 are closely related Dbl-homology GTP exchange factors (GEFs) for Rho GTPases [2].
• Compensation between Vav-1 and Vav-2 in B cell development and antigen receptor signaling [2].
• B and T lymphocytes develop normally in mice lacking the guanine nucleotide exchange factor Vav-2 [3].
• These studies show the importance of Vav-2 in humoral immune responses and B cell maturation [3].

Biological context of Vav2

• Consistent with their distinct substrate targets, it was found that constitutively activated versions of Vav and Vav2 caused distinct transformed phenotypes when expressed in NIH 3T3 cells [4].
• Transfection of NIH3T3 cells with expression vectors containing vav2 deletions demonstrate that elimination of 183 amino terminal residues of Vav2 is sufficient to activate its oncogenic potential [5].
• Vav2-induced transformation is characterized by the appearance of foci composed of cells in which cytokinesis and karyokinesis are uncoupled [5].
• Signal transduction through Vav-2 participates in humoral immune responses and B cell maturation [3].
• In contrast, the constitutive expression of the Vav-2 oncoprotein in rodent fibroblasts leads to major alterations in cell morphology and to highly enlarged cells in which karyokinesis and cytokinesis frequently are uncoupled [6].

Anatomical context of Vav2

• It is also possible that two other Vav family molecules, Vav2 and Vav3, are involved in NK cell activation [7].
• To investigate whether Vav isoforms have redundant or unique functions in regulating adhesion and migration, we investigated the properties of Vav1-deficient and Vav2-deficient macrophages [8].
• Both Vav1-deficient and Vav2-deficient cells have a smaller adhesive area; yet, only Vav1-deficient cells have a reduced migration speed, which coincides with a lower level of microtubules [8].
• Finally, Vav2-transformed NIH 3T3 cells showed up-regulated levels of Rac-GTP [4].
• Vav-2-deficient mice are also defective in their ability to switch immunoglobulin class, form germinal centers and generate secondary immune responses to TD antigens [3].

Associations of Vav2 with chemical compounds

• Vav1-mutant mice generate defective humoral immunoglobulin G (IgG) responses following administration of low doses of LPS but respond normally to higher doses, while mice lacking both Vav1 and Vav2 manifest defective responses even after a high dose of LPS [9].
• In vivo, wild-type Vav-2 is activated oncogenically by tyrosine kinases, an effect enhanced further by co-expression of RhoA [6].

Other interactions of Vav2

• This phosphorylation event is conserved in Vav-2 and Vav-3, the other two members of the Vav family [10].

References