Attaching and effacing (AE) adhesion is associated with the pathogenesis of enteropathogenic Escherichia coli (EPEC) and rabbit diarrheogenic E. coli (RDEC-1). Although RDEC-1 provides an animal model for investigating pathophysiology of EPEC infection, RDEC-1 does not adhere to human cell lines, thereby limiting in vitro investigation. Therefore, transformed RDEC-1 strains expressing adhesins derived from human diarrheogenic E. coli were studied. These adhesins promoted AE adhesion of RDEC-1 and led to the accumulation of alpha-actinin aggregates in the cytoplasm of infected cells. Furthermore, these strains induced host signal transduction pathways, resulting in tyrosine phosphorylation of host proteins and an intracellular elevation of calcium. These results demonstrate that RDEC-1 and EPEC stimulate similar signal transduction pathways in infected epithelial cells, thus lending additional support for the use of RDEC-1 as a model for the study of human EPEC infection.