Proto-Oncogene Vav (VAV1) Protein

Background

VAV1 is a guanine nucleotide exchange factor (GEF) that activates Rho family GTPases, such as Rac1 and Cdc42, by facilitating the exchange of GDP for GTP. It is primarily expressed in hematopoietic cells, where it plays a critical role in T-cell receptor (TCR) and B-cell receptor (BCR) signaling, cytoskeletal rearrangement, and immune cell activation. VAV1 acts as a signaling scaffold, linking tyrosine kinases to downstream effectors that regulate cell migration, adhesion, and polarization. It is essential for lymphocyte development, antigen receptor signaling, and immune responses. Dysregulation of VAV1 is associated with autoimmune diseases, impaired immune cell function, and certain cancers, including T-cell leukemia, where it promotes abnormal proliferation and survival. Knockout studies reveal defects in T-cell activation, impaired immune responses, and defective cytoskeletal organization, highlighting its critical role in immune signaling, cytoskeletal dynamics, and lymphocyte function.