Vav1 is a guanine nucleotide exchange factor (GEF) that is physiologically active in the hematopoietic system. It contains multiple domains characteristic of signal-transducing proteins and functions as a key regulator in T/B lymphocyte antigen-receptor signaling, promoting actin polymerization, immunological synapse formation, T cell activation and differentiation, and cytokine production [1,3]. It is also involved in pathways like the activation of calcium flux, extracellular signal-regulated kinase (ERK), and the nuclear factor kappaB (NF-κB) transcription factor [3].

Vav1-deficient mice have shown that Vav1 plays a crucial role in thymic selection events, including positive and negative selection. Vav1-deficient T cells are defective in TCR-induced proliferation and cytokine synthesis [3]. In transgenic mouse models, overexpression of Vav1 in different tissues led to the development of B-cell lymphomas, suggesting a cross-talk between epithelial cells expressing Vav1 and lymphocytes [2]. Also, co-expression of Vav1 and K-RasG12D in type II pneumocytes of mice increased malignant lung cancer lesions, indicating Vav1's contribution to lung tumor development [4].

In conclusion, Vav1 is essential for normal hematopoietic function, especially in T cell-related processes. Studies using gene-knockout (KO) and transgenic mouse models have revealed its significant role in autoimmune and chronic inflammatory diseases, as well as in cancer development, including B-cell lymphoma and lung cancer. These models have provided valuable insights into the biological functions of Vav1 and its potential as a therapeutic target.