PH domain which appears to induce conformational changes in DOCK and thus allow binding to Rac. Signalling downstream of Dock2 Like other DOCK-A and DOCK-B subfamily proteins Dock2 GEF activity is specific for Rac. Leukocytes express both Rac1 and Rac2 and Dock2 has been shown to bind and promote nucleotide exchange on both of these isoforms. Rac isoforms regulate a multitude of processes in leukocytes and studies so far have shown that Dock2-dependent Rac activation regulates the neutrophil NADPH oxidase and is also important for chemotaxis in neutrophils, lymphocytes and plasmacytoid dendritic cells. Dock2-dependent NADPH oxidase activation was reported in response to the soluble agonist fMLP, which acts via G protein-coupled receptors in neutrophils. Dock2-dependent chemotaxis has been reported in response to the chemokines CXCL12/SDF-1 in T lymphocytes, CXCL13/BLC in B lymphocytes and CCL19/ELC in thymocytes (immature lymphocytes) emigrating from the thymus as well as CCL21/SLC in ex vivo plasmacytoid dendritic cells. In neutrophil chemotaxis Dock2 signals downstream of the C5a and CXCL8/IL-8 receptors. Additional receptors which signal through Dock2 include the T cell receptor/TCR and EDG1, a sphingosine-1-phosphate (S1P) receptor. The HIV-1 protein Nef is able to constitutively activate Dock2 in T lymphocytes which disrupts chemotaxis and immunological synapse formation thereby inhibiting the antiviral immune response. Interactions Dock2 has been shown to interact with CRKL. References Further reading External links