Elmo (engulfment and cell motility) proteins share similarity to C. elegans CED-12. The C. elegans genes ced-2, ced-5, ced-10 and ced-12, and their mammalian homologs, CRKII, DOCK1, RAC1 and ELMO, mediate cytoskeletal rear-rangements during phagocytosis of apoptotic cells as well as cell motility. Elmo1 associates with DOCK 180 and may influence phagocytosis and effect cell shape changes. Src family kinase-mediated tyrosine phosphorylation of Elmo1 influences signaling through Elmo1/Crk/DOCK 180 pathways. Elmo2 interacts directly with Rho G in a GTP-dependent manner and forms a ternary complex with DOCK 180 to induce activation of Rac 1. The Rho G-Elmo2-DOCK 180 pathway is required for activation of Rac 1 and cell spreading mediated by integrin, as well as for neurite outgrowth induced by nerve growth factor. Elmo3 acts in assocation with DOCK 180 and Crk II and may be required in complex with DOCK 180 to activate Rac/Rho small GTPases.