CORTACTIN ASSOCIATES WITH THE CELL-CELL JUNCTION PROTEIN ZO-1 IN BOTHDROSOPHILA AND MOUSE

Cortactin is an actin filament-binding protein localizing at cortical regions of cells and a prominent substrate for Src family protein-tyro sine kinases in response to multiple extracellular stimuli. Human cort actin has been identified as a protein product of a putative oncogene, EMS1. In this report, we describe the identification of a Drosophila homolog of cortactin as a molecule that interacts with Drosophila ZO-1 using yeast two-hybrid screening. Drosophila cortactin is a 559-amino acid protein highly expressed in embryos, larvae, and pupae but relat ively underexpressed in adult flies. Deletion and substitution mutant analyses revealed that the SH3 domain of Drosophila cortactin binds to a PXXP motif in the proline-rich domain of Drosophila ZO-1. Colocaliz ation of these proteins at cell-cell junction sites was evident under a confocal laser-scanning microscope. In vivo association was confirme d by coimmunoprecipitation of cortactin and ZO-1 from Drosophila embry o lysates. We also demonstrate an association for each of the murine h omologs by immunoprecipitation analyses of mouse tissue lysates. Our p revious work has demonstrated the involvement of ZO-1 in a signaling p athway that regulates expression of the emc gene in Drosophila. The po tential roles of the cortactin.ZO-1 complex in cell adhesion and cell signaling are discussed.