Identification of EPS8 as a Dvl1-associated molecule

Dishevelled (Dsh) is involved in both Wingless (Wg) and Frizzled (Fz) signa ling pathways. To further determine the function of Dsh, we have performed yeast two-hybrid screening and isolated several genes encoding the molecule s associated with the PDZ domain of Dvl1, one of the murine Dsh homologs. D uring the screening, we found that EPS8, which is a substrate for activated EGF receptor (EGFR), specifically interacted with Dvl1. This interaction w as also confirmed in vitro. Through transfection studies, we observed the m utual action between Dvl1 and EPS8. Dvl1 was hyperphosphorylated in the pre sence of EPS8, whereas the tyrosine phosphorylation of EPS8 by activated EG FR was inhibited in the presence of Dvl1. Immunohistochemistry showed that Dvl1 and EPS8 expression overlap in particular tissues during organogenesis . These results indicate that interaction between Dvl1 and receptor tyrosin e kinase signal plays certain roles in developmental events. (C) 1999 Acade mic Press.