Phospholipase C-gamma 1 (PLC-gamma 1) is a lipase that hydrolyzes PIP2 to generate two second messengers, IP3 and DAG, By using the yeast two-hybrid system, we identified the translational elongation factor-1 alpha (EF-1 alpha) as a binding protein of PLC-gamma 1 from the human B-lymphocyte library, Direct interaction between EF-1 alpha and PLC-gamma 1 was confirmed by the in vitro binding experiment using purified PLC-gamma 1, Furthermore, from the in vitro binding experiment, we could demonstrate that the carboxyl terminal region of EF-1 alpha is involved in the interaction with PLC-gamma 1, and that both SH2 and SH3 domains of PLC-gamma 1 are required for the interaction with EF-1 alpha. In vivo interaction between EF-1 alpha and PLC-gamma 1 was confirmed by the immunoprecipitation experiment using anti-EF-1 alpha antibody. The interaction between EF-1 alpha and PLC-gamma 1 was enhanced by EGF-treatment, Taken together, we suggest that EF-1 alpha might play a role in PLC-gamma 1-mediated signal transduction