Disease relevance of VIL2

• Ezrin was coimmunoprecipitated with merlin from lysates of human U251 glioma cells and from COS-1 cells transfected with cDNA encoding for merlin isoform I. The interaction was further studied and the association domains were mapped with the yeast two-hybrid system and with blot overlay and affinity precipitation experiments [1].
• Neurofibromatosis 2 tumor suppressor protein colocalizes with ezrin and CD44 and associates with actin-containing cytoskeleton [2].
• Similarly, moesin and ezrin mRNA levels were reduced in lung adenocarcinoma [3].
• Ezrin is expressed by many tumor cell lines; however, little is known about the function of ezrin in tumorigenesis and metastasis [4].
• These results suggest that there is a relationship between high expression of ezrin and metastatic potential of pancreatic carcinomas [4].
• Matrigel invasion of the androgen-insensitive prostate cancer cell lines PC-3 and LNCaP-R is also dependent on ezrin [5].

Psychiatry related information on VIL2

• The mechanism underlying cannibalism involved a complex framework, including lysosomal protease cathepsin B activity, caveolae formation, and ezrin cytoskeleton integrity and function [6].
• However, further data are needed before ezrin can be considered in clinical decision-making about osteosarcoma patients [7].

High impact information on VIL2

• A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor [8].
• A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor [9].
• VIL2 and SIX1 expression was enhanced in human RMS tissue, significantly correlating with clinical stage [10].
• Transduction of the signal induced by GAS binding to CD44 on the keratinocyte surface involved Rac1 and the cytoskeleton linker protein ezrin, as well as tyrosine phosphorylation of cellular proteins [11].
• The ERM (ezrin, radixin and moesin) family of proteins are linkers that tether actin microfilaments to the plasma membrane [12].

Chemical compound and disease context of VIL2

• In response to epidermal growth factor (EGF) the microvillar core protein ezrin is phosphorylated transiently to a high level on tyrosine residues in human epidermoid carcinoma A431 cells [13].
• An affinity-purified antibody prepared against this peptide segment (p81) is shown here to cross-react with a homologous region of the human T-cell leukemia virus type I (HTLV-I) envelope glycoprotein, raising the interesting possibility that the envelope glycoprotein of HTLV-I can interact with the beta hIL-2 receptor [14].
• Estradiol-induced ezrin overexpression in ovarian cancer: a new signaling domain for estrogen [15].

Biological context of VIL2

• Finally, overexpression of the C-terminal threonine phosphorylation site mutant of ezrin has a dominant inhibitory effect on PKCalpha-induced cell migration [16].
• Ezrin is a downstream effector of trafficking PKC-integrin complexes involved in the control of cell motility [16].
• Here we show that cells overproducing a mutant form of ezrin in which Tyr-353 was changed to a phenylalanine (Y353F) undergo apoptosis when assayed for tubulogenesis [17].
• Ezrin self-association involves binding of an N-terminal domain to a normally masked C-terminal domain that includes the F-actin binding site [18].
• It is concluded that ezrin regulates cell-cell and cell-matrix adhesion, by interacting with cell adhesion molecules E-cadherin and beta-catenin, and may thus play an important role in the control of adhesion and invasiveness of cancer cells [19].

Anatomical context of VIL2

• Ezrin protein subfamily members act as linkers between the plasma membrane and the cytoskeleton [20].
• We have studied the interaction of moesin and ezrin with the vascular cell adhesion molecule (VCAM)-1 during leukocyte adhesion and transendothelial migration (TEM) [21].
• VCAM-1 interacted directly with moesin and ezrin in vitro, and all of these molecules colocalized at the apical surface of endothelium [21].
• We have investigated ezrin function in tubulogenesis of a kidney-derived epithelial cell line, LLC-PK1 [17].
• Polarization and interaction of adhesion molecules P-selectin glycoprotein ligand 1 and intercellular adhesion molecule 3 with moesin and ezrin in myeloid cells [22].

Associations of VIL2 with chemical compounds

• Both in vitro and in vivo interaction studies indicated that phosphorylation of serine 518 promotes heterodimerization between merlin and ezrin, an event suggested to convert merlin from a growth-suppressive to a growth-permissive state [23].
• Exposure of this domain required unfolding ezrin with sodium dodecyl sulfate or expressing the domain as part of a truncated protein [18].
• The adenosine 2b receptor is recruited to the plasma membrane and associates with E3KARP and Ezrin upon agonist stimulation [24].
• Immunofluorescence localization of two ezrin-binding proteins was performed in cryosections of rat eyes of various ages and in monolayers extracted with the detergent Triton X-100 and fixed in paraformaldehyde [25].
• Identification of the two major epidermal growth factor-induced tyrosine phosphorylation sites in the microvillar core protein ezrin [13].
• We found that the region -87/-32 containing consensus Sp1 (-75/-69) and AP-1 (-64/-58) binding sites is crucial for VIL2 promoter activity in esophageal carcinoma cells (EC109) derived from ESCC [26].

Physical interactions of VIL2

• Furthermore, our data indicate that moesin is identical to the 77-kDa band that copurifies with ezrin in its isolation from human placenta [Bretscher, A. (1989) J. Cell Biol. 108, 921-930] [27].
• As shown earlier for the human homolog of NHERF, we also found that the cytoskeletal protein ezrin binds to the carboxyl-terminal domain of E3KARP [28].
• In these cells, the mutated ezrin did not co-localize or co-immunoprecipitate with CD95 [29].
• Our biochemical study verifies that ezrin binds to PALS1 via its N terminus and is co-localized with PALS1 to the apical membrane of gastric parietal cells [30].
• The S100P binding site is located in the N-terminal domain of ezrin and is accessible for interaction in dormant ezrin, in which binding sites for F-actin and transmembrane proteins are masked through an association between the N- and C-terminal domains [31].

Enzymatic interactions of VIL2

• Akt2 phosphorylates ezrin to trigger NHE3 translocation and activation [32].
• Ezrin was constitutively tyrosine phosphorylated in wild-type and CD45-deficient Jurkat T cells, but not in Lck-deficient cells [33].
• CD95/phosphorylated ezrin association underlies HIV-1 GP120/IL-2-induced susceptibility to CD95(APO-1/Fas)-mediated apoptosis of human resting CD4(+)T lymphocytes [34].
• Ezrin was then found to be homologous to p81 and to be phosphorylated on tyrosine in response to EGF (Gould, K. L., J. A. Cooper, A. Bretscher, and T. Hunter. 1986. J. Cell Biol. 102:660-669) [35].
• In A431 cells in which cell surface ruffling was stimulated by EGF, myosin VI was phosphorylated and recruited into the newly formed ruffles along with ezrin and myosin V [36].

Co-localisations of VIL2

• Here we show that human T cells that are susceptible to CD95-mediated apoptosis, exhibit a constitutive polarized morphology, and that CD95 colocalizes with ezrin at the site of cellular polarization [37].

Regulatory relationships of VIL2

• Ezrin controls the macromolecular complexes formed between an adapter protein Na+/H+ exchanger regulatory factor and the cystic fibrosis transmembrane conductance regulator [38].
• These two PDZ (postsynaptic density protein [PSD-95]/disc large [DLG]-A/ZO-1) domain proteins had a similar polarized distribution and high resistance to detergent extractability, indicative of cytoskeletal association, both in primary cultures of rat RPE and in a clonal RPE-J cell line expressing high levels of transfected ezrin [25].
• Based on these and additional results, we propose a model whereby dormant ezrin can be activated to bind EBP50 on its NH2-terminal end and F-actin on its COOH-terminal end [39].
• Here we report the identification of the tyrosine phosphorylation sites in ezrin using bacterially expressed protein as a substrate for in vitro phosphorylation with the EGF receptor [13].
• Altogether, these observations indicate that ezrin is able to trigger FAK activation in signaling events that are not elicited by cell-matrix adhesion [40].

Other interactions of VIL2

• This association is mediated by the actin-linking proteins moesin and ezrin, which directly interact with Syk in an ITAM-dependent manner [41].
• Type III delivered ExoS ADP-ribosylated moesin and ezrin (and/or radixin) in cultured HeLa cells [42].
• Immunoprecipitation and immunoblotting confirm the specific interactions of NHERF with the full-length CFTR and with ezrin in vivo [38].
• NHE3 kinase A regulatory protein E3KARP binds the epithelial brush border Na+/H+ exchanger NHE3 and the cytoskeletal protein ezrin [28].
• We also found that ezrin associates with E3KARP in vivo [43].

Analytical, diagnostic and therapeutic context of VIL2

• Bands of 78- and 81-kd were identified as moesin and ezrin by Western blot analysis [22].
• Co-immunoprecipitation established that in PS120 cells, NHE3 bound to full-length NHERF(1-355), the C-terminal domain, NHERF(147-355), and NHERF(1-325), which lacks the proposed ezrin-binding domain [44].
• The interaction of both proteins with ezrin and gluthathione-S-transferase (GST)-ezrin fusion proteins was analyzed by SDS-PAGE and immunoblot [25].
• Radiation hybrid mapping has refined the location of ezrin to the interval between D6S442 and D6S281 [45].
• Immunofluorescence microscopy of cultured cells and tissues revealed that EBP50 colocalizes with actin and ezrin in the apical microvilli of epithelial cells, and immunoelectron microscopy demonstrated that it is specifically associated with the microvilli of the placental syncytiotrophoblast [46].

References