Association of Ezrin with Intercellular Adhesion Molecule-1 and -2 (ICAM-1 and ICAM-2)

Heiska, Leena; Alfthan, Kaija; Grönholm, Mikaela; Vilja, Pekka; Vaheri, Antti; Carpén, Olli

doi:10.1074/jbc.273.34.21893

Cited by 291 publications

(247 citation statements)

References 60 publications

Supporting

Mentioning

237

Contrasting

Unclassified

Order By: Relevance

“…Leukocyte TEM is inhibited after the inactivation of endothelial cells' Rho protein function (Adamson et al, 1999), thereby suggesting a proactive role for ICAM-1 signaling/cytoskeletal interactions in facilitating TEM. In agreement with these lines, the intracellular domain of ICAM-1 can bind to a variety of molecules, such as ␣-actinin (Carpen et al, 1992), ␤-tubulin, GAPDH (Federici et al, 1996), and ezrin (Heiska et al, 1998). These proteins all have the potential to perform signaling functions.…”

Section: Introductionmentioning

confidence: 74%

“…ICAM-1 has also been known to be associated with ezrin/radixin/moesin (ERM) family members, i.e., ezrin and moesin (Heiska et al, 1998;Barreiro et al, 2002). To test whether truncation of the intracellular domain alters the association of ICAM-1 with the proteins mentioned above, the subcellular distribution of ICAM-1, actin, ezrin, and moesin was analyzed by confocal microscopy in COS-7 cells transfected with wt-IC1_GFP or IC1⌬CTD_GFP.…”

Section: The Distribution and Dynamic Movements Of Icam-1 On Transfecmentioning

confidence: 99%

See 1 more Smart Citation

RKIKK Motif in the Intracellular Domain Is Critical for Spatial and Dynamic Organization of ICAM-1: Functional Implication for the Leukocyte Adhesion and Transmigration

Lee

et al. 2007

MBoC

View full text Add to dashboard Cite

No direct evidence has been reported whether the spatial organization of ICAM-1 on the cell surface is linked to its physiological function in terms of leukocyte adhesion and transendothelial migration (TEM). Here we observed that ICAM-1 by itself directly regulates the de novo elongation of microvilli and is thereby clustered on the microvilli. However, truncation of the intracellular domain resulted in uniform cell surface distribution of ICAM-1. Mutation analysis revealed that the C-terminal 21 amino acids are dispensable, whereas a segment of 5 amino acids ( 507 RKIKK 511 ) in the NH-terminal third of intracellular domain, is required for the proper localization and dynamic distribution of ICAM-1 and the association of ICAM-1 with F-actin, ezrin, and moesin. Importantly, deletion of the 507 RKIKK 511 significantly delayed the LFA-1-dependent membrane projection and decreased leukocyte adhesion and subsequent TEM. Endothelial cells treated with cell-permeant penetratin-ICAM-1 peptides comprising ICAM-1 RKIKK sequences inhibited leukocyte TEM. Collectively, these findings demonstrate that 507 RKIKK 511 is an essential motif for the microvillus ICAM-1 presentation and further suggest a novel regulatory role for ICAM-1 topography in leukocyte TEM.

show abstract

Section: Introductionmentioning

confidence: 74%

Section: The Distribution and Dynamic Movements Of Icam-1 On Transfecmentioning

confidence: 99%

RKIKK Motif in the Intracellular Domain Is Critical for Spatial and Dynamic Organization of ICAM-1: Functional Implication for the Leukocyte Adhesion and Transmigration

Lee

et al. 2007

MBoC

View full text Add to dashboard Cite

show abstract

“…The amino-terminal half of the ERM protein is about 85% homologous, whereas homology in the carboxy-terminal half is about 65% (Mangeat et al, 1999). The ERM proteins bind to actin filaments at their carboxy-terminal domain (Algrain et al, 1993;Henry et al, 1995;Turunen et al, 1994), and to several integral membrane proteins, such as CD43, CD44, and ICAM-1, -2, and -3, and so on, at their aminoterminal domains (Heiska et al, 1998;Mangeat et al, 1999;Yonemura et al, 1998). The ERM proteins are involved in a variety of cellular functions, such as cell adhesion, migration, and the organization of cell surface structures (Bretscher et al, 1997;Mangeat et al, 1999;Martin et al, 1995;Sato et al, 1991Sato et al, , 1992.…”

Section: Discussionmentioning

confidence: 99%

Altered Expression of the ERM Proteins in Lung Adenocarcinoma

Tokunou

Niki²,

Saitoh

et al. 2000

Laboratory Investigation

View full text Add to dashboard Cite

SUMMARY:Radixin is a member of the ERM (ezrin/radixin/moesin) protein family that is proposed to function as a membrane-cytoskeletal linker. Using differential display analysis, we have identified radixin as a gene down-regulated in primary lung adenocarcinoma. Real-time quantitative reverse transcription polymerase chain reaction confirmed that radixin mRNA was decreased, both in 10 early-stage bronchioloalveolar carcinomas and in 16 invasive lung adenocarcinomas, by 69% (p ϭ 0.0002) and 82% (p Ͻ 0.0001), respectively, compared with 9 nontumor lung tissues. Similarly, moesin and ezrin mRNA levels were reduced in lung adenocarcinoma. Immunohistochemistry confirmed that cancer cells expressed very little radixin and moesin, whereas non-neoplastic alveolar and bronchiolar epithelial cells, and endothelial cells, including those within the tumor stroma, were consistently positive for these two proteins. Ezrin was localized in the apical surface of non-neoplastic bronchiolar and alveolar epithelial cells and, in contrast to radixin and moesin, the majority of tumor cells retained expression of ezrin. Localization of ezrin was altered in a significant proportion of tumor cells: whereas tumor cells forming lumina displayed membranous staining on the apical side, tumor cells with disorganized structures were either negative or diffusely positive for ezrin in the cytoplasm. Furthermore, a fraction of tumor cells invading the stroma in a scattered manner were strongly positive for ezrin. In conclusion, expression of radixin and moesin is down-regulated in lung adenocarcinoma, including early-stage bronchioloalveolar carcinoma. An intriguing implication of this finding is that these two genes may function as tumor suppressors in lung adenocarcinoma oncogenesis. Although structurally related to radixin and moesin, ezrin may have a distinct function in tumor-cell invasion. (Lab Invest 2000, 80:1643-1650.O f the various malignant tumors, lung cancer is the most common cause of cancer death worldwide. However the biological behavior of lung cancer is not fully characterized, and the outcome of surgical treatment remains unsatisfactory. Identification of genes that are involved in tumorigenesis and in the progression of lung cancer will be required to formulate more effective therapies. One approach to the identification of such genes is to use differential display analysis (Bauer et al, 1993;Liang et al, , 1993Sager et al, 1993;Yoshikawa et al, 1998).Radixin is a member of the ERM (ezrin/radixin/ moesin) family of proteins (Mangeat et al, 1999;Sato et al, 1992), which was first isolated as a constituent of adherence junctions in rat liver (Tsukita and Hieda, 1989). Ezrin was first purified as a component of intestinal microvilli that is tyrosine-phosphorylated by epidermal growth factor receptor (EGFR; Bretscher, 1989), and moesin was originally identified as a heparin-binding protein (Lankes and Furthmayr, 1991). The amino-terminal half of the ERM protein is about 85% homologous, whereas homology in the carboxy-terminal hal...

show abstract

“…In response to upstream activation of Rho, Rho kinase phosphorylates a threonine residue in the C-terminal domain of ERM proteins, disrupting the head-to-tail association that maintains the closed conformation (Fig 1B). Once ERM proteins adopt the open conformation, their FERM domain can associate with the cytoplasmic segment of cell-adhesion receptors-such as CD44 and ICAM-and their C-terminal domain can interact with actin filaments, regulating the organization of the cortical cytoskeleton [38,41,42].…”

Section: Merlin Structure and Modificationsmentioning

confidence: 99%

Merlin: a tumour suppressor with functions at the cell cortex and in the nucleus

et al. 2012

View full text Add to dashboard Cite

Inhibition of proliferation by cell-to-cell contact is essential for tissue organization, and its disruption contributes to tumorigenesis. The FERM domain protein Merlin, encoded by the NF2 tumour suppressor gene, is an important mediator of contact inhibition. Merlin was thought to inhibit mitogenic signalling and activate the Hippo pathway by interacting with diverse target-effectors at or near the plasma membrane. However, recent studies highlight that Merlin pleiotropically affects signalling by migrating into the nucleus and inducing a growth-suppressive programme of gene expression through its direct inhibition of the CRL4 DCAF1 E3 ubiquitin ligase. In addition, Merlin promotes the establishment of epithelial adhesion and polarity by recruiting Par3 and aPKC to E-cadherin-dependent junctions, and by ensuring the assembly of tight junctions. These recent advances suggest that Merlin acts at the cell cortex and in the nucleus in a similar, albeit antithetic, manner to the oncogene β-catenin.

show abstract

Association of Ezrin with Intercellular Adhesion Molecule-1 and -2 (ICAM-1 and ICAM-2)

Cited by 291 publications

References 60 publications

RKIKK Motif in the Intracellular Domain Is Critical for Spatial and Dynamic Organization of ICAM-1: Functional Implication for the Leukocyte Adhesion and Transmigration

RKIKK Motif in the Intracellular Domain Is Critical for Spatial and Dynamic Organization of ICAM-1: Functional Implication for the Leukocyte Adhesion and Transmigration

Altered Expression of the ERM Proteins in Lung Adenocarcinoma

Merlin: a tumour suppressor with functions at the cell cortex and in the nucleus

Contact Info

Product

Resources

About