Journal of Cell Science id opopaiyioio ,-ipopae[PtdIns(4,5) 4,5-bisphosphate phosphatidylinositol also through It and 50). to indirectly binding CD43, binds ( or EBP50 CD44, as (ICAMs) such either as scaffold proteins interacts such domain adhesion receptors FERM intercellular membrane The with 2011). directly Fehon, and Neisch point an (four through FERM domain F-- binding N-terminal C-terminal a an to domains: linked domain one-ezrin–radixin–) three of consist that iiigcls n elcl dein Beshre l,2002; 2008). in al., Rossy, and et furrow Niggli (Bretscher 2002; cleavage adhesions al., uropods, et the cell–cell Gautreau filopodia, and filament- ruffles, cells, as actin membrane dividing dynamic such and of structures 2010). lamellipodia formation al., membrane the et (Fehon containing pathways to polarity contribute transduction cell as actin They and signal the migration act in and cell proteins regulating participate receptors surface and of cell , family between linkers (ERM) reversible ezrin/radixin/moesin The Introduction GEFs. Vav through of junctions phenotype adherens role important the of an formation reverses words: plays and depletion Key radixin polarity that GEF indicate epithelial Vav results Rac1-mediated Our Indeed, regulating activity. by GEFs. Rac1 nucleotide migration on guanine Vav knockdown cell Rac of radixin promoting of radixin of activity Analysis in the effect the RhoA. for the or required affects reduces Cdc42 is and radixin not knockdown Rac1 that radixin but and cancer suggests Rac1 Rac1, of active breast (GEFs) actin by constitutively activity MDA-MB-231 factors depletion alters by the in moesin, exchange induced increases also observed that or also depletion were to depletion ezrin Radixin similar Radixin effects not phenotype. junctions. is Similar but knockdown cells adherens moesin. radixin, radixin-depleted by and of that phenotype mediated ezrin and The phosphorylated adhesion cells, cells. active cell–cell cancer of prostate processes. and distribution these PC3 area in and of radixin spread organization, migration of cell involvement for and the increases required Ezrin about interference cytoskeleton. known is actin is RNA radixin the little that to but migration, receptors show cell membrane we and plasma polarization Here link cell that in proteins implicated adaptor been are have moesin moesin and radixin ezrin, proteins ERM The Summary 10.1242/jcs.094383 doi: 3310–3319 125, ß Science Cell of Journal 2012 March 8 Accepted ( correspondence for *Author 2 1 Valderrama Ferran adhesion Rac1 cell–cell through and migration cell regulates Radixin 3310 yooi rcino el n h idn ie o plasma for are to binding sites proteins by ERM binding induced PtdIns(4,5) ‘closed’ masked. changes the conformational are through inactive F-actin and activated N- and cells an proteins the of membrane to the in in fraction found binds are they cytosolic exist domain conformation this In C-terminal al., domain. can FERM et terminal the Oshiro al., proteins 1995; where et al., Gautreau conformation, et ERM 2000; Nakamura al., 1998; 1998). al., et et Gautreau Matsui 2002; 2002; al., et (Bretscher aauae l,19;Rc ta. 00 uae l,2011). al., et 2000; Suda al., 2010; et al., Gautreau et 2003; Roch 1995; al., and radixin al., et in et (Brown T564 Nakamura moesin] ezrin, in in [T567 T558 residue threonine terminal adl iiino eladMlclrBohsc,Kn’ olg odn e utsHue u’ aps odnS11L UK UK 1UL, 0RE, SE1 SW17 London London Campus, Terrace, Guy’s Cranmer House, London, Hunt’s of New University London, George’s, College St King’s Sciences, Biophysics, Biomedical Molecular of and Division Cell of Division Randall 02 ulse yTeCmayo ilgssLtd Biologists of Company The by Published 2012. zi,rdxnadmei r lsl related closely are moesin and radixin Ezrin, P R rtis h Tae ci yokltn ahrn elmgain elcl adhesion cell–cell migration, cell cadherin, cytoskeleton, actin GTPase, Rho proteins, ERM 2 n usqetpopoyaino osre C- conserved a of phosphorylation subsequent and [email protected] 1,2 uag Thevapala Subangi , a hlcldmi Fhne l,2010; al., et (Fehon domain -helical ) , 0kaproteins 80-kDa 2 n neJ Ridley J. Anne and P 2 ] R rtisas idt h yolsi oano the of domain cytoplasmic the to proteins 2002). bind al., ERM et also Yonemura activated 1997; proteins al., et in ERM Shaw to 2007; enriched al., leading et microvilli (Auvinen phosphorylation, of C-terminal stimulating induction by and/or Tkhsie l,19) nteohrhn,Ro n Rac and RhoA PtdIns(4,5) hand, of other levels the the increasing by On activity RhoGDI 1998). ERM with stimulate al., compete would et interaction this (Takahashi report this that In suggested 1998). Dbl al., is RhoGEF et Takahashi it the 2007; al., between studies et interaction (Prag vitro radixin direct In and a apical 2007). reported al., the also et in (D’Angelo have changes cells morphological epithelial induce of for region GEF to a Rac1, 6), and member been domain RhoG RhoGEF has with G domain Ezrin homology family (pleckstrin containing 2005). PLEKHG6 with Couchman, reducing interact to and promoting reported thereby (Dovas consequently proteins, activation and GTPases their ERM with with 1997). interaction phosphorylation al., RhoGDI associate et by Mackay 2004; can or Ridley, and RhoGDI Ivetic (GDIs) nucleotide 1996; al., inhibitors et (Hirao dissociation guanine activating GDP binding by GTPase regulated by to also GDP-bound are by GTPases Rho inactivated inactive activated Some (GAPs). and proteins an cycle (GEFs) are factors GTPases, and exchange Rho They GTP-bound 2007). active conformation. Fehon, an and migration and between Hughes polarity cell 2009; of regulators (Hall, key are 2009; which al., GTPases, et Parisiadou 2001; al., 2011). et al., 1998; Ng et al., Yamane et 2000; Matsui al., 2008; al., et et Nakamura Hebert 2009; C, al., al., et ERM kinase et Belkina regulate (Baeyens 2010; threonine protein to this reported of phosphorylation the been through have function of families MRCK members and ROCK including kinases, Several R rtiscnatbt ptemaddwsra fRho of downstream and upstream both act can proteins ERM 1, * eerhArticle Research P 2 Journal of Cell Science ie el tie o -ci Fg F rfo nlsso cells of analysis from or 1F) from (Fig. quantified F-actin either for cells, stained radixin- control cells of to fixed area addition, spread compared In cell cells the 4). in cells depleted and increase control fourfold 3 a in Movies observed we material observed supplementary regions localised 1E; discrete and (Fig. small in the ruffles than rather membrane ruffling periphery, membrane whole persistent on their showed around also and they cells; plastic control than uncoated shown). not on (data obtained surfaces fibronectin-coated substrate were or the collagen-I results of independent following similar be migration 4 as of to inhibition with appeared The suppression supplementary observed 2). radixin and 1D; cells, 1 (Fig. Movies radixin siRNA-transfected material targeting control 38% siRNAs approximately of independent of speed that migration a of had cells PC3 depleted eea acrtps nldn rsaecne.Frexample, For cancer. prostate including types, cancer to C- several the leads of 2010). T-lymphocytes dephosphorylation al., et via (Cernuda-Morollon in threonine proteins terminal activation ERM al., et of Rac1 Tsuda inactivation 2004; al., Finally, et Lee 1999; 2004). al., et Pozo by enhanced (del activity is RhoA interaction this and CD44 receptor transmembrane ssnl el ihamsnhmlmrhlg,admigrate and morphology, 1.34 mesenchymal of migrate a speed and mean with grow a with normally supplementary cells cells single PC3 1C; 2). (Fig. as and 1 microscopy Movies time-lapse material moesin by or 1A) (Fig. ezrin generated each of siRNAs levels were different the moesin affect 4 1B). not (Fig. and did by ezrin depletion down Radixin Radixin, knocked supplementary S1). efficiently in by Table (sequences cells siRNA material PC3 with carcinoma-derived transfection prostate transient in ERM depleted we expression migration, cell protein in radixin of role the elucidate To migration cell regulates Radixin Results activity. Rac1 altering by a to morphology from adhesions migratory transition cell–cell Our a with the changes. morphology regulate these epithelial levels non-migratory radixin mediates that depletion, indicate radixin results which by Rac1, activated that demonstrate focal is We cytoskeleton, contacts. actin cell–cell area and the spread contacts of increased and reorganization shape with is severely cell inhibition concomitant in depletion This change cells. a radixin not PC3 by cancer accompanied that has prostate radixin show of for migration we model impairs role Here a described. migration, metastasis been cell in experimental studied extensively an 2009). breast in al., promoting et in (Valastyan metastasis implicated On been 2011). and has in cancer al., radixin decrease et hand, neoplasia normal (Bartholow other slight the adenocarcinomas in intraepithelial a in showed levels expression prostate radixin tissues moesin adenocarcinoma grade prostatic and high the radixin a prostate, Recently, in 2006). analysing al., phosphorylation et (Chuan study invasion LNCaP ezrin line, cell cell of cancer Androgen-induced prostate regulation 2005). hormonal prostate al., grade requires et high Valdman prognosis, both al., et 2004; (Pang in adverse adenocarcinoma prostate expression and with neoplasia of intraepithelial correlated levels been high showing has expression ezrin aii-eltdclswr lte ihamr iclrshape circular more a with flatter were cells Radixin-depleted lhuhtefntoso zi n osnhv been have moesin and ezrin of functions the Although in investigated been has proteins ERM of expression The elmgainwsaaye ytakn el nmovies in cells tracking by analysed was migration Cell 6 0.04 m /iue ncnrs,radixin- contrast, In m/minute. u uta1%o oto el hwdasmlrphenotype similar a showed cells control of that 13% 1). flat observed and (Table a circular We in were just cells shape cells. knockdown but flat radixin knockdown the circular, of radixin a 90% almost had and therefore that We control cells population cells. both of whole radixin-depleted defined number to the a the shape in quantified with flat cells similar phenotype some a migratory observed with most a we Although had edge, 1F). cells (Fig. leading area control of cell depletion the affect contrast, not of In did shown). ezrin or not moesin (data movies time-lapse in iso ci iaetbnls(i.2) cie C-terminally Active, 2A). (Fig. bundles filament the actin at localised mainly of that contacts tips focal was around larger distribution to reorganization uniform periphery cell a the actin from 2004) This Schaller, 2001; (Schaller, membrane. paxillin cell marker contact focal plasma the re-localisation of and a by accompanied the cytoskeleton localised to more mainly cells, had actin close control cells than bundles PC3 the filament radixin-depleted actin peripheral that to was observed knockdown We changes adhesions. radixin by whether investigated accompanied we for required migration, are dynamics cell adhesion cell and cytoskeleton actin Since contact focal and distribution filament actin regulates Radixin 3) ncnrlP3clsNcdei a predominantly at was localisation N-cadherin some with cells cytoplasm PC3 the throughout Fig. control distributed and material In (supplementary did establishing expression S3B). knockdown E-cadherin E-cadherin radixin not for induce and but not S3A), N-cadherin important Fig. and express material Shapiro cells (supplementary be 2010; PC3 al., junctions, 2009). et to Weis, (Millan adherens cell–cell contacts known of cell–cell in maintaining distribution change are the radixin-regulated which analysed more this their in we for investigate with to adhesion basis order contact In the 3B). maintained (Fig. detail over h movie: cells 16 each over radixin-depleted of neighbour(s) was duration of the This during 90% maintained 6). other that each cells cells and with of control 5 contact proportion the than Movies determining by contacts material quantified cell–cell radixin-depleted supplementary that stable 3A; (Fig. apparent more was formed it cells movies, time-lapse contacts From (supplementary cell–cell increases specific depletion Radixin PC3-cell not is S2). Fig. phenotype material indicating the cells, cancer breast that on MDA-MB-231 p-ERM in surface of western dorsal accumulation the by and bundles determined filament actin as peripheral p-ERM, of S1). Fig. levels material total (supplementary blotting alter it control although not the distribution, p-ERM of did regulates 12% 2C). clearly only (Fig. height therefore whereas that Radixin height at distribution cell F-actin/p-ERM the the similar had of of cells 20% 80% p-ERM top and the than F-actin in punctate for more positive were that cells 2006). radixin-depleted epithelial al., indicated more et of a Quantification Lan have characteristic cells 2010; phenotype. PC3 al., a radixin-depleted et that 2B), suggests (Fehon (Fig. This cells F-actin epithelial punctate of of microvilli more distribution to a similar dorsal cells, had radixin-depleted the in p-ERMs surface to dorsal contrast, the on In distribution localise In protrusions. 2008). cell Rossy, often and other filopodia and to localised primarily were (Niggli p-ERMs (p-ERMs) cells, PC3 lamellipodia control and proteins ruffles membrane ERM phosphorylated aii elto iial nue elsraig increased spreading, cell induced similarly depletion Radixin aii ncl irto n dein3311 adhesion and migration cell in Radixin Journal of Cell Science xeiet.Aayi fvrac AOA a efre oass h infcneo h eut hw nec rp.Sbeunl untsmulti (*** Dunnet’s populations a down Subsequently knocked graph. and each control in between shown significant results were the differences 10 of the bar: significance whether Scale the determine Scal cells. assess cells. to control knockdown to used of radixin performed was that in was test arrowheads to (ANOVA) comparison and relative variance cells expressed of control is Analysis in area experiments. arrows spread by ( The indicated 50 siRNA. siRNA. bar: are control control Scale ruffles or indicated. 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B C el eetasetdwt iNst aii,VvGF Vv,Vv n a3,bt aii n a Es rcnrlsRA fe 72 After siRNA. control or GEFs, Vav and radixin both Vav3), and Vav2 (Vav1, GEFs Vav radixin, to siRNAs with transfected were cells PC3 ) ( A C el eetasetdwt h niae iNst aii,erno osno control or moesin or ezrin radixin, to siRNAs indicated the with transfected were cells PC3 ) eecya el icuigfbolssadastrocytes) (Li and junctions adherens fibroblasts N-cadherin-mediated (including form However, frequently E-cadherin. cells re-express not do morphology, mesenchymal they epithelial that more fact a the of a despite acquisition to has similar expressed. adhesion both depletion are MDA-MB-231 moesin moesin and and PC3 ezrin or in though morphology even simply ezrin cells, cell not not on are effect Only but isoforms. profound depletion 3 depletion the radixin of radixin or expression and tissue-selective area moesin by cell explained ezrin, in different of increase the radixin- that effects an indicate in results by Our migration contacts. accompanied by of radixin cadherin-mediated acts is inhibition it of cells The that regulates depleted known and radixin activity. adhesion, that Rac1 is cell–cell time altering and first little migration the shape, for moesin, cell show and we Here ezrin function. to Compared 6). Discussion (Fig. activation cell Rac1-mediated GEF knockdown for GEF Vav required radixin the Vav is spreading. that of upon depletion indicate radixin observed absence following results was these the activity Together, in Rac1 in depletion change No fcl ra n xrsino osiuieyatv a1induces Rac1 active constitutively of expression and The area, these. cell of increase resemble knockdown-induced radixin in since the Rac1 to formed inhibits on knockdown dependent junctions Rac1 are likely the depletion radixin thus are by induced and changes cells 2010), al., PC3 et radixin-depleted Zhu 2001; al., et aii elto nue hne nP3cl hp and shape cell PC3 in changes induces depletion Radixin m m. .Values v. lations Journal of Cell Science ucin Gble l,20) nzbaih osnadthe and endothelial moesin regulate zebrafish, adherens both In of 2004). positioning VE-cadherin al., and the endothelium-specific et formation al., (Gobel by lumen et junctions for accompanied (Saotome required villi, junctions is of cell–cell In this elongated 2004). fusion to ezrin of epithelium, in linked intestinal appearance been mouse results the previously in deficiency not example, has For process. radixin but adhesion, depletion. radixin upon cell observed in activity since increase Rac1 the Tiam1, and following for required than size increased were rather they was and GEFs GEFs knockdown Vav radixin Vav to of due phosphorylation radixin-depleted of junctions tyrosine be in might activity downstream adherens cells Rac1 implicated PC3 increased regulating The been 2009). in have 2006). (Rivard, al., 3-kinases Vav et and phosphoinositide (Fukuyama Tiam1 Rac1 to in Both implicated signalling been also junction have GEFs adherens Vav 2004). al., et epithelial (Malliri MDCK cells in assembly RacGEF junction example, adherens For stimulates been Tiam1 assembly. have junction thus RacGEFs adherens adherens and in Several of implicated level 2007), cells. high radixin-depleted al., the in et explain junctions Ray could 2009; activity al., Rac1 increased et (Hage is junctions established adherens maintaining well and inducing in contacts. Rac1 cell–cell of at role The accumulation N-cadherin and spreading cell condition each between significant were (* used differences was the test whether comparison determine multiple to Bonferroni’s a Subsequently, results. the of and Rac1 (graph). means total experiments are independent and Values three active from assays. of activity pull-down relative shown of by is quantification determined blot were was western Cells activity siRNAs. representative Rac1 control A and or hours, Vav3) 72 and after Vav2 lysed (Vav1, GEFs Rac1 Vav of to siRNAs increase radixin-dependent the mediate activity. GEFs Vav 6. Fig. P ohernadmei r mlctdi euaigcell–cell regulating in implicated are moesin and ezrin Both , .5 *** 0.05; C el eetasetda niae ihsRA oradixin, to siRNAs with indicated as transfected were cells PC3 anradtselegans Caenorhabditis P , 6 0.001). ...AOAwspromdt sestesignificance the assess to performed was ANOVA s.e.m. h igeEMpoenerm-1 protein ERM single the , rgeso Cie l,20) ofrltl skonaotradixin Moesin about known is 2004). little with far So correlating (Hunter, 2009). cancers, al., some et (Cui progression in progression upregulated also and is influences expression and cancers, survival of variety tumour a in aggressiveness tumour for PC3 in localisation N-cadherin regulates cells. that radixin given that cochlea, whether observe the know we in to localisation interesting humans cadherin-23 be (Kitajiri in affects would to radixin deafness it cells thus to are due and lead hair 2008), mutations (Muller, deaf which on Cadherin-23 2004). become projections stereocilia, al., et apical also cochlear filament-based mice of actin Radixin-null degeneration (Kikuchi membranes 2002). underlying progressive canalicular decrease bile The al., a apical fertile. to et the relate are in could it microvilli and although in 2007), unclear, normally al., therefore grow et is (Fukumoto defect mice mice the the of dependent and background is genetic phenotype the this the into However, it on 2002). secrete al., to et unable (Kikuchi are in bile they bilirubin because of possibly levels blood, high their accumulate mice (Zhu radixin-deficient vessels and blood of 2010). development al., during et formation lumen Vlsyne l,20) elto ftemR3 agt radixin, targets miR-31 the integrin of and microRNA RhoA Depletion the 2009). models of al., animal in et target metastasis (Valastyan a cancer breast is inhibits it which miR-31, interestingly although cancer, in pcfe nsplmnaymtra al 1 a sduls otherwise unless used was S1) (as Table siRNA 2 material were radixin samples supplementary knockdown, and indicated. transfection radixin in using after involving esiRNA specified hours experiments or 14 siRNA For medium nM complete collected. material Medium to 50 antibiotics. changed supplementary with without medium was were transfected complete in in vav3 reverse (Invitrogen) specified and 2000 were vav2 Lipofectamine are of Cells vav1, sequences mixture for S1. sequence) (a Table their mRNA esiRNA same Sigma-Aldrich; Scientific); the from target (Thermo all Dharmacon that from siRNAs were siRNAs All transfections DNA and siRNA 100 FCS, 10% with supplemented mM 25 CO glutamine containing (5% RPMI penicillin in units/ml mM 100 2 grown and were streptomycin, cells and cancer prostate Hepes DU145 and PC3 reagents and lines Cell Methods and Materials epciey.Ecp hnseiial ttd l h hmclraet were reagents chemical NA931, the and all NA934 stated, Sigma-Aldrich. no. specifically from (cat. obtained when GE-Healthcare HRP-anti- Except respectively). from A21126, respectively). HRP-anti-mouse and were A11103 and Alexa antibodies A11008, anti-rabbit, rabbit secondary no. anti-mouse 488 (cat. 633 Fluor Invitrogen Fluor Alexa from Alexa Invitrogen and respectively). anti-mouse, A22284, from 546 visualized and Fluor phalloidin were A22283 filaments Alexa-Fluor-633-labelled no. actin (cat. or G-8795); respectively); Alexa-Fluor-546- no. sc-16408-R, (cat. Vav from with and 610154, ARH03-A); sc-132 Sigma-Aldrich Cdc42 no. no. from and (cat. 05-389); (cat. GAPDH Cruz Cytoskeleton no. Santa 610134 from from (cat. phospho-Vav RhoA 610404, Millipore and 07-1466); from no. 610921, (cat. 23A8 Millipore no. clone p120-catenin, Rac1 (cat. respectively); 2541, E-cadherin, Laboratories and and 3672 2466, MLC Transduction N-cadherin, 3142, phospho-ERM, 3145, no. moesin, (cat. respectively); ezrin, Signalling R3653); Cell from no. phospho-paxillin (cat. Sigma-Aldrich from oee.Ordt r ossetwt oefrrdxnin to radixin contribute for could role which a migration, with progression. known, cell cancer consistent not cancer is are promoting data three these Our of however. each The of 2010). contribution al., et relative (Valastyan metastasis suppressing in expression acrclswr rw nDE otiig2 MHpsad2m glutamine mM 2 and Hepes 100 mM FCS, 25 10% containing with DMEM supplemented in grown were cells cancer 5 CO (5% nrae zi xrsini elkonponsi marker prognostic well-known a is expression ezrin Increased liver, mouse in membranes canicular bile to localises Radixin aii ncl irto n dein3317 adhesion and migration cell in Radixin 2 ,37 ˚ ) nioiswr bandfo h olwn ore:radixin sources: following the from obtained were Antibodies C). a oehrpeooisteefcso miR-31 of effects the phenocopies together 5 m /lsrpoyi,ad10uism penicillin units/ml 100 and streptomycin, g/ml 2 ,37 ˚ ) D-B21breast MDA-MB-231 C). b ctnnfo BD from -catenin m g/ml Journal of Cell Science n41%plarlmd es(nirgn,taserdt nitrocellulose to transferred (Invitrogen), antibodies. indicated gels the with blotted polyacrylamide and membranes 4–12% on upeetr aeilaalbeoln at http://jcs.biologists.org/lookup/suppl/doi:10.1242/jcs.094383/-/DC1 online available material Supplementary F.V.). to grant St (start-up and London RE/08/003]; of number University [grant Heart George’s British Excellence London of College Centre King’s A.J.R.); Foundation to Sciences number Research (Prize Life Foundation Cancer the [grant Bettencourt-Schueller for for the UK A.J.R.); Institute to Research Ludwig funding (core Cancer the A.J.R.]; by to supported C6620/A8833 was work This the in included Funding the images the to of their and some for of London manuscript acquisition of manuscript. their the University the for George’s during laboratory of St help Ridley at development the Facility of the Microscopy members during the to insights grateful are We Acknowledgements MgCl assay 1mM mM 7.5; 10 activation pH NaCl, Tris-HCl, RhoA mM mM 50 the 500 buffer: lysis Cytoskeleton or EDTA; following and the assay (Upstate/Millipore using respectively) instructions activation Inc, manufacturer’s and the Rac/Cdc42 scrapped to were control the according siRNA with for or radixin processed against siRNA with treated Cells assays activity GTPase Rho 40 a using Inc.) 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NA 1.3 m gof ae . enl . am . ih,K n ek,A. Menke, and K. Giehl, I., Baum, K., Meinel, B., Hage, vtc .adRde,A J. A. Ridley, and A. Ivetic, A. Hall, Go M. Arpin, and D. Louvard, A., Gautreau, Y. Takai, M. and Arpin, and D. M. Louvard, A., Inagaki, Gautreau, T., Kawakatsu, H., Ogita, T., Fukuyama, utr .W. K. Hunter, G. R. Fehon, and C. S. Hughes, Y., Takai, T., Sasaki, M., Monden, S., Yonemura, T., Kondo, N., Sato, M., Hirao, He Tsukita, H., Yamagishi, M., Hata, A., Tamura, N., Itoh, S., Kikuchi, K., Fukumoto, ayn,N,Hra,S,Vromn . ie,M n oe,N. Morel, and M. Rider, D., Vertommen, S., Horman, N., Baeyens, A. Vaheri, and N. Kivi, E., Auvinen, References atoo,T . hnrn .R,Bcc,M .adPrai .V. A. Parwani, and J. M. Becich, R., U. Chandran, L., T. Bartholow, e oo .A,VcneMnaae,M,Tjdr . erdr .M and R. M. J. Couchman, J. and A. Serrador, Dovas, R., Tejedor, M., Vicente-Manzanares, A., M. Pozo, del ekn,N . i,Y,Ho .J,Krsym,H n hw S. Shaw, and H. Karasuyama, J., J. Hao, Y., Liu, V., N. 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Barrett, V., ¨bel, inligi leucocytes. in signalling pancreatic in IQGAP1 to cells. binding erm-1. carcinoma via junctions linker adherens E-cadherin-mediated membrane-cytoskeleton inhibits the requires elegans Cell C. Dev. in morphogenesis signaling. growth cell and Biol. organization actin Cell cortical Opin. of Curr. Yang and Yin the suppressor: 10 bear. to brought finally genetics of power pathway. phosphati- signaling of Rho-dependent 51. involvement and possible turnover association: dylinositol membrane protein/plasma S. moesin) Tsukita, and S. Tsukita, 14. plasma the at monomers to oligomers from membrane. transition phosphorylation-induced a 3-kinase- c-Src-Rap1-phosphatidylinositol the pathway. through Vav2 cadherin by Rac of Activation Mrp3. of levels expression different Acta to due mice radixin-deficient S. Tsukita, and S. ppoi nJra cells. Jurkat in Fas-mediated apoptosis regulates phosphorylation ezrin-radixin-moesin Rho-ROCK-dependent proteins. ERM of role the dniiainadfntoa mlcto faRokns-eedn moesin-EBP50 artery. kinase-dependent C1530-C1540. Rho noradrenaline-stimulated a in of interaction implication functional and Identification cells. epithelial human in PIPK and deinmlclsadctseea R opnnsi lymphocytes. T in components ERM cytoskeletal Immunol. and molecules adhesion Sa muoitceia tiigo aii n osni rsai adenocarcinoma. prostatic in moesin Pathol. and Clin. radixin BMC of staining Immunohistochemical fRofml Taeactivities. GTPase family Rho of factor exchange nucleotide guanine novel api the cells. RhoG-dependent epithelial with promotes ezrin PLEKHG6 of Interaction (2007). lrsMrls A. Flores-Morales, rearrangement cytoskeletal regulates and phosphorylation. lymphocytes ERM resting through in kinase ERM major rfln npnrai acrwt n ihu yp oemetastasis. node lymph without and 124 with cancer pancreatic in profiling ezrin. by mediated ONE J. A. 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