Additional functions of Vav3 in distinct tissues are listed below.
Nervous system: NGF-induced neurite outgrowth in PC12 cells requires Vav3-mediated activation of Rac. This process involves P13K activation which occurs upstream of Vav3 (Aoki et al., 2005). Vav3 is also important for neuronal migration during development (Khodosevich et al., 2009). Additionally, Vav3 knockout mice show defects in Purkinje cell dendrite branching, granule cell migration and survival. Functionally the animals show deficiencies in motor coordination and gaiting consistent with a role for Vav3 in neuronal guidance, cerebellar development and function (Quevedo et al., 2010).
Skeletal system: Studies in osteoclasts support a role for Vav3 in mediating proper bone deposition. Specifically, Vav3 deficient osteoclasts exhibit abnormalities in actin cytoskeletal rearrangements, cell spreading, and resorptive activities. Consistent with the actions of Vav3 on integrin signaling, the osteoclast defects were found to be due to impaired integrin engagement. Further, Vav3 deficient mice have increased bone density and are refractory to PTH-mediated bone resorption (Faccio et al., 2005).
Cardiovascular system: An important role for Vav3 in maintaining proper cardiovascular homeostasis was suggested by experiments performed in Vav3 null mice. These mice exhibited many symptoms of cardiovascular dysfunction including tachycardia, hypertension and cardiovascular remodeling. Consistent with these symptoms, the mice also exhibited a high degree of sympathetic tone including elevated circulating levels of catecholamines and renin-angiotensin-aldosterone hyperactivity, resulting in progressive loss of both cardiovascular and renal homeostasis (Sauzeau et al., 2006).
Vascular smooth muscle: Vav3 is both necessary and sufficient for rat vascular smooth muscle cell proliferation. These effects occur through a Rac-1 dependent mechanism, involving the effector Pak 1 (Toumaniantz et al., 2010).
Platelets: Consistent with a role for Vav3 in mediating integrin-based responses, Vav3 and Vav1 together are required for collagen exposure-mediated PLC activation in platelets. This signaling pathway occurs through the major platelet integrin alphaIIbbetaIII (Pearce et al., 2004).
Angiogenesis: Mice deficient in both Vav3 and Vav2 show reduced endothelial migration in response to the presence of tumor cells. Additionally Vav2 and Vav3 were found to be necessary and sufficient for Eph A receptor-mediated angiogenesis both in vitro and in vivo (Hunter et al., 2006).