Overexpressed Ly-6A.2 mediates cell-cell adhesion by binding a ligand expressed on lymphoid cells.

Bamezai, Anil; Rock, Kenneth L.

doi:10.1073/pnas.92.10.4294

Cited by 73 publications

(60 citation statements)

References 21 publications

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“…Previous studies suggested the involvement of Ly-6A/E in T-cell activation (19,20) and development (21). Ly-6A/E and Ly-6C have been shown to regulate cell adhesion (14,15), but the in vivo functions of Ly-6 family are unknown with the exception of CD59 and urokinase-type plasminogen activator receptor. CD59 functions as a membrane inhibitor of reactive lysis, and failure to express CD59 is related to the pathogenesis of paroxysmal nocturnal hemoglobinuria (PNH).…”

Section: Discussionmentioning

confidence: 99%

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Intectin, a Novel Small Intestine-specific Glycosylphosphatidylinositol-anchored Protein, Accelerates Apoptosis of Intestinal Epithelial Cells

Kitazawa

Nishihara

Nambu

et al. 2004

Journal of Biological Chemistry

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Intestinal epithelial cells undergo rapid turnover and exfoliation especially at the villus tips. This process is modulated by various nutrients especially fat. Apoptosis is one of the important regulatory mechanisms of this turnover. Therefore, identification of the factors that control epithelial cell apoptosis should help us understand the mechanism of intestinal mucosal turnover. Here, we report the identification of a novel small intestine-specific member of the Ly-6 family, intectin, by signal sequence trap method. Intectin mRNA expression was exclusively identified in the intestine and localized at the villus tips of intestinal mucosa, which is known to undergo apoptosis. Intectin mRNA expression was modulated by nutrition. Intestinal epithelial cells expressing intectin were more sensitive to palmitate-induced apoptosis, compared with control intestinal epithelial cells, and such effect was accompanied by increased activity of caspase-3. Intectin expression also reduced cell-cell adhesion of intestinal epithelial cells.Intestinal epithelial cells originate from stem cells at the base of the crypt and migrate along the crypt-villus axis toward the intestinal lumen. When intestinal epithelial cells reach the luminal surface at the villus tips, they finally exfoliate into the lumen, and their cell cycle is terminated with a life span of only 3-5 days (1, 2). This constant and rapid turnover of intestinal mucosa is essential for maximal nutrient absorption, adaptation to changes in diet, and repair of mucosal injury (3).Apoptosis plays an important role in maintaining the physiological integrity of many tissues. In the intestine, apoptosis is a key regulator for the turnover of intestinal mucosa, and apoptotic intestinal epithelial cells have been detected at the villus tips of the small intestine and the colonic luminal surface (4 -6). However, the one or more underlying mechanisms of this process have not been elucidated. In this regard, it is important to identify the factors that control intestinal epithelial cell apoptosis to understand the mechanism of intestinal mucosal turnover.The present study was designed to identify a small intestinederived protein or secretory protein modulated nutritionally that is involved in the control of intestinal epithelial cell apoptosis. Using the efficient signal sequence trap (SST) 1 method (7), we identified a novel small intestine-specific GPI-anchored protein, intectin, which showed distinct localization at the villus tips of intestinal mucosa and accelerated fatty acid-induced apoptosis of intestinal epithelial cells. EXPERIMENTAL PROCEDURESCloning of Intectin cDNA-Poly(A) ϩ RNAs were extracted from the small intestinal epithelium of C57BL/6J mice under three feeding conditions; ad libitum, 24-h fasting, and 24-h fasting followed by 24-h feeding, and from the small intestinal epithelium of ad libitum-fed db/db mice. Equal amount of poly(A) ϩ RNA from each group was pooled and used as the template to synthesize complementary DNA (cDNA). To selectively clone the gen...

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Section: Discussionmentioning

confidence: 99%

“…Intectin Reduces Cell-to-Cell Adhesion-Previous studies suggested that some members of the Ly-6 family are involved (14,15). Therefore, we conducted a cell aggregation assay using parental CHO cells (CHO) and CHO cells stably expressing intectin (CHO-intectin).…”

Section: Intectin Mrna Expression Is Modulated By Nutritional Status-mentioning

confidence: 99%

Intectin, a Novel Small Intestine-specific Glycosylphosphatidylinositol-anchored Protein, Accelerates Apoptosis of Intestinal Epithelial Cells

Kitazawa

Nishihara

Nambu

et al. 2004

Journal of Biological Chemistry

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“…Although most of the identity among these genes lies outside the coding region of the mature protein, all Ly-6SF members are expected to assume very similar three-dimensional structures based on the 10 highly conserved cysteine residues (30). Ly-6A/E and Ly-6C have been proposed to act as adhesion molecules by binding cell surface ligands (25,32,33). The conserved structure of the Ly-6SF may allow more than one family member to associate with a given ligand molecule.…”

Section: Discussionmentioning

confidence: 99%

“…Gene knockouts have only been analyzed for Ly-6A/E, which suggested that the Ag may have an inhibitory role in regulating cell activation (24). Other studies have suggested roles in cell adhesion in lymphocytes (25) and bone marrow stroma (26) and in T cell Ag-specific immune responses (27). Overexpression of Ly-6A/E can permit CD4 ϩ T cells to be positively selected in the absence of MHC expression (28).…”

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confidence: 99%

Ly-6I, a New Member of the Murine Ly-6 Superfamily with a Distinct Pattern of Expression

Pflugh

Maher

Bothwell

2000

The Journal of Immunology

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A new member of the mouse Ly-6SF, designated Ly-6I, has been isolated as a gene homologous to a segment of the Ly-6C gene. A single allelic difference in the mature protein sequence was identified, which is similar to other Ly-6SF members. Ly-6I mRNA has been detected in a wide range of tissues and cell lines, and a rabbit polyclonal Ab has been used to determine that Ly-6I protein is present at a low constitutive level on cell lines from several different lineages. In contrast to Ly-6C and Ly-6A/E, the Ly-6I gene is only weakly responsive to IFNs. Expression in vivo is most abundant on bone marrow populations and is coexpressed with Ly-6C on granulocytes and macrophages. However, Ly-6I is also expressed on immature B cell populations that do not express Ly-6C. Expression on mature B cells in spleen is uniformly low. Similarly, Ly-6I is expressed on TCRlow/int, but not TCRhigh, thymocytes. Ly-6I is re-expressed on Ly-6Chigh T cells in the periphery. Thus, Ly-6I may be a useful marker to define maturation stages of both T and B lymphocytes as well as subsets of monocytes and granulocytes.

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“…8 -11 A role in cell adhesion has been described for the human E48 antigen and the mLy-6A.2 and mLy-6C antigens. 7,[12][13][14] The human E48 antigen was also shown to be involved in cell signaling, resulting in increased selectin-mediated adhesion, when using MAb E48 as a surrogate ligand. 15,16 The first Ly-6 ligand, described for the murine ThB antigen, has only recently been identified.…”

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confidence: 99%

Characterization of the human Ly‐6 antigens, the newly annotated member Ly‐6K included, as molecular markers for head‐and‐neck squamous cell carcinoma

Dalen

Dongen

Smeets

et al. 2002

Intl Journal of Cancer

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The E48 antigen is a successfully explored molecular marker for the diagnosis and therapy of HNSCC. The applicability of E48 as an HNSCC-associated antigen, however, is restricted due to its heterogeneous expression in 30% of tumors; and identification of additional target antigens is therefore desired. E48 belongs to the Ly-6 antigen family, comprising a group of highly homologous, low m.w., GPIanchored surface proteins, of which some show tissue-restricted expression patterns. To identify novel human HNSCC-associated Ly-6 members with squamous cell-associated expression patterns, we performed comprehensive gene-screening consisting of BLAST searches within GenBank databases, followed by expression analysis. Using this approach, the Ly-6K gene could be annotated as a novel member of the human Ly-6 family. Expression of the human Ly-6 genes E48, Ly-6K, PSCA, GML, RIG-E, G6C and Ly-6H was prescreened by qualitative RT-PCR and subsequently analyzed by quantitative RT-PCR in normal keratinocytes, HNSCC cell lines, normal mucosa, HNSCC tumors as well as normal peripheral blood and bone marrow cells. PSCA was highly expressed in normal mucosa, but 100-fold decreased expression was seen in HNSCC. For Ly-6H, GML and G6C, no or very low expression was observed in keratinocytes and HNSCC. Expression of RIG-E was high in normal and malignant squamous cells and in peripheral blood and bone marrow cells, thus limiting its applicability as an HNSCC-associated marker. In contrast, besides the E48 gene, the Ly-6K gene also appeared to be selectively expressed in HNSCC and normal squamous cells. Moreover, expression of Ly-6K was shown in HNSCC cell lines, in which no E48 expression could be detected. These data justify further evaluation of Ly-6K as potential target antigen for the diagnosis and therapy of HNSCC.

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Overexpressed Ly-6A.2 mediates cell-cell adhesion by binding a ligand expressed on lymphoid cells.

Cited by 73 publications

References 21 publications

Intectin, a Novel Small Intestine-specific Glycosylphosphatidylinositol-anchored Protein, Accelerates Apoptosis of Intestinal Epithelial Cells

Intectin, a Novel Small Intestine-specific Glycosylphosphatidylinositol-anchored Protein, Accelerates Apoptosis of Intestinal Epithelial Cells

Ly-6I, a New Member of the Murine Ly-6 Superfamily with a Distinct Pattern of Expression

Characterization of the human Ly‐6 antigens, the newly annotated member Ly‐6K included, as molecular markers for head‐and‐neck squamous cell carcinoma

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