The microvillar core protein Ezrin is a tyrosine-phosphorylated protein foundin epidermal growth factor-stimulated A-431 carcinoma cells. Ezrin is phosphorylated transiently to a high level on Tyrosine residues 146 and 354. One of the sites, Tyrosine 146, lies in the amino-terminal region of homology that is common to the protein 4.1-Talin-Ezrin protein family. This tyrosine residue and its vicinal amino acids are conserved throughout the family which includes Radixin, Moesin and the two phosphotyrosine phosphatases, PTP H1 and PTP MEG. Another phosphorylation site is Tyrosine 354, which is localized within the α-helical domain of Ezrin. Cytoplasmic signaling may result in activation of Ezrin in tyrosine phosphorylation and this suggests that Ezrin has qualities that might play a role in modulation of cell shape and adhesion..