The C. elegans genes ced-2, ced-5, and ced-10, and their mammalian homologs 
crkII, dock180, and rac1, mediate cytoskeletal rearrangements during 
phagocytosis of apoptotic cells and cell motility. Here, we describe an 
additional member of this signaling pathway, ced-12, and its mammalian homologs, 
elmo1 and elmo2. In C. elegans, CED-12 is required for engulfment of dying cells 
and for cell migrations. In mammalian cells, ELMO1 functionally cooperates with 
CrkII and Dock180 to promote phagocytosis and cell shape changes. CED-12/ELMO-1 
binds directly to CED-5/Dock180; this evolutionarily conserved complex 
stimulates a Rac-GEF, leading to Rac1 activation and cytoskeletal 
rearrangements. These studies identify CED-12/ELMO as an upstream regulator of 
Rac1 that affects engulfment and cell migration from C. elegans to mammals.