Identification of 14-3-3zeta as an EGF receptor interacting protein

The 14-3-3 proteins are known to interact with a number of proteins involved in the regulation of cell signaling. Here, we describe an association of 14-3-3zeta with the epidermal growth factor receptor (EGFR) that is rapidly induced by EGF. The 1028-EGFR truncated mutant which lacks the cytoplasmic tail from amino acids 1029-1186 identified the binding site for 14-3-3 to be between amino acid 1028 and the receptor carboxyl terminus. Mutational deletion of serine residues 1046, 1047, 1057 and 1142 did not inhibit EGF-induced 14-3-3 association with the receptor. Immunofluorescence microscopy indicated an EGF-induced co-localization of EGFR and HA-14-3-3zeta along the plasma membrane. Our finding adds to the growing complexity of EGF receptor signaling and indicates a role for 14-3-3 proteins in EGF receptor signaling or regulation.