Anti-Phospho-Ezrin: Rabbit Ezrin, Phospho-Tyr354 Antibody

BACKGROUND The ERM family consists of three closely related proteins, Ezrin, radixin, and moesin (ERM proteins). Ezrin (82 kDa) was enriched in microvilli of cells. Radixin (80 kDa) is a component of adherent junctions. Moesin (75 kDa) was isolated from bovine uterus abundant in smooth muscle cells as a heparin-binding protein.  Ezrin serves as an intermediate between the plasma membrane and the actin cytoskeleton. In epithelial cells, Ezrin is required for the formation of microvilli and membrane ruffles on the apical pole. Along with PLEKHG6, it is required for normal macropinocytosis. Ezrin plays a key role in cell surface structure adhesion, migration and organization.  It has been implicated in various human cancers.¹

 

There are active (insoluble) and inactive (soluble) forms of ERM proteins in terms of their cross-linking activity inside cells. The cross-linking activity of ERM proteins between actin filaments and plasma membranes is dynamically regulated. In ERM proteins, the N-terminal FERM domain is followed by an extended alpha-helical domain and a charged C-terminal domain, which includes a consensus sequence motif for actin binding. The N- and C-terminal halves of ERM proteins mutually interact intramolecularly and suppress their actin filament and membrane binding activities. Some activation signal may release this suppression to activate ERM proteins inside cells.² Two molecular events have been shown to generate and/or maintain the active form of ERM proteins: PIP2 binding to their N-terminal domains and phosphorylation of their C-terminal threonine residue. It has been shown that PIP2 is a key factor for the activation of ERM proteins.  EGF stimulated phosphorylation of Tyr146 and Tyr354 of Ezrin in A431 cells.³ Secretion/stimulation in gastric parietal cells was reported to induce serine/threonine phosphorylation of Ezrin. Functional analyses suggested that the C-terminal threonine phosphorylation maintains ERM proteins in the active state by suppressing the intramolecular interaction. Rho signaling pathway has been reported to activate the C-terminal threonine phosphorylation of ERM proteins. ERM proteins, once activated, can activate Rho, which again activates ERM proteins as a positive feedback system. ERM proteins can be dephosphorylated and inactivated, resulting in their cytoplasmic translocation with concomitant microvillar breakdown.⁴
 

REFERENCES  

1. Sato, N. et al: J. Cell Sci. 103:131-43, 1992
2. Bretscher, A.: Curr. Opin. Cell Biol.  11:109-16, 1999
3. Tsukita, S. & Yonemura,S.: J. Biol. Chem. 274:34507-10, 1999
4. Kondo, T. et al: J. Cell Biol. 139:749-58, 1997