scholarly journals Increased synthesis and expression of H-2 antigens on thymocytes as a result of radiation leukemia virus infection: a possible mechanism for H-2 linked control of virus-induced neoplasia.

1978 ◽  
Vol 147 (2) ◽  
pp. 470-487 ◽  
Author(s):  
D Meruelo ◽  
S H Nimelstein ◽  
P P Jones ◽  
M Lieberman ◽  
H O McDevitt
Keyword(s):  
Virus Infection ◽  
Cell Surface ◽  
Leukemia Virus ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Electrophoretic Analysis ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Altered Expression ◽  
Thymus Cells

Previous studies from this laboratory have mapped resistance and/or susceptibility to radiation-induced leukemia virus (RadLV)-induced neoplasia to the H-2D region. H-2 linked effects on virus replication can be detected subsequent to the initial virus infection, and clear-cut differences in numbers of virus infected thymus cells can be detected as early as 5 wk after RadLV inoculation. Rapid increases in cellular synthesis and cell surface expression of H-2 antigens are detectable immediately after virus inoculation. These changes have been studied by immunofluorescence, absorption, cell surface iodination followed by sodium dodecyl-sulfate-polyacrylamide gel electrophoresis, and two dimensional gel electrophoretic analysis of internally labeled lymphocyte proteins. Expression of H-2K molecules is significantly increased in cells of susceptible and resistant animals. However, significant increases in expression of H-2D antigens occurs only on thymus cells from resistant strains (H-2Dd). Transformed cells of resistant and susceptible H-2 haplotypes adapted to tissue culture lack detectable H-2 antigens as determined by serological absorption studies. It is argued that altered expression of H-2 antigens plays a very significant role in the mechanism of host defense to virus infection.

scholarly journals A role for elevated H-2 antigen expression in resistance to neoplasia caused by radiation-induced leukemia virus. Enhancement of effective tumor surveillance by killer lymphocytes.

1979 ◽  
Vol 149 (4) ◽  
pp. 898-909 ◽  
Author(s):  
D Meruelo
Keyword(s):  
Virus Infection ◽  
Leukemia Virus ◽  
Antigen Expression ◽  
Cell Surface Expression ◽  
Target Cells ◽  
Cell Mediated Immunity ◽  
Altered Expression ◽  
Radiation Induced ◽  
Low Levels

Resistance to neoplasia caused by radiation-induced leukemia virus (RadLV) is mediated by gene(s) in the H-2D region of the major histocompatibility complex. The previous observation that rapid increases in cellular synthesis and cell-surface expression of H-2 antigens are detectable immediately after virus inoculation has suggested that altered expression of H-2 antigens may play a significant role in the mechanism(s) of host defense to virus infection. This concept is supported by the following observations. First, cell-mediated immunity against RadLV transformed or infected cells can be detected with ease when H-2-positive target cells are used in the cell-mediated lympholysis (CML) assay. (Although RadLV transformed cells obtained from overtly leukemic animals and maintained in tissue culture are H-2 negative, these cells can regain their H-2 phenotype by in vivo passage in normal animals. The H-2-negative cells are poor targets in a CML assay.) Second, resistant mice develop greater numbers of effectors when infected with RadLV than do susceptible mice. Third, injection of normal (uninfected) thymocytes into syngeneic recipients of resistant or susceptible H-2 type does not stimulate a CML response. However, injection of RadLV infected thymocytes from resistant mice produces a vigorous CMI response, and such thymocytes elicit the strongest response at a time when both H-2 and viral antigen expression is elevated. By contrast, injection of infected thymocytes from susceptible mice, which express viral antigens, but low levels of H-2 antigens, does not stimulate a CML reaction. These findings may explain the easier induction of leukemia found by many investigators when virus is inoculated into neonatal mice and the preferential thymus tropism of some oncogenic type-C RNA virus. Cells expressing very low levels of H-2, such as thymocytes, may serve as permissive targets for virus infection because they lack an important component (H-2 antigens) of the dual or altered recognition signal required to trigger a defensive host immune response.

Processing and stability of type IIc sodium-dependent phosphate cotransporter mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria

2012 ◽  
Vol 302 (9) ◽  
pp. C1316-C1330 ◽  
Author(s):  
Sakiko Haito-Sugino ◽  
Mikiko Ito ◽  
Akiko Ohi ◽  
Yuji Shiozaki ◽  
Natsumi Kangawa ◽  
...  
Keyword(s):  
Cell Surface ◽  
Polyacrylamide Gel Electrophoresis ◽  
Surface Expression ◽  
Confocal Imaging ◽  
Hypophosphatemic Rickets ◽  
Cell Surface Expression ◽  
Opossum Kidney ◽  
Ok Cells ◽  
Er Retention ◽  
The Impact

Mutations in the apically located Na+-dependent phosphate (NaPi) cotransporter, SLC34A3 (NaPi-IIc), are a cause of hereditary hypophosphatemic rickets with hypercalciuria (HHRH). We have characterized the impact of several HHRH mutations on the processing and stability of human NaPi-IIc. Mutations S138F, G196R, R468W, R564C, and c.228delC in human NaPi-IIc significantly decreased the levels of NaPi cotransport activities in Xenopus oocytes. In S138F and R564C mutant proteins, this reduction is a result of a decrease in the Vmax for Pi, but not the Km. G196R, R468W, and c.228delC mutants were not localized to oocyte membranes. In opossum kidney (OK) cells, cell surface labeling, microscopic confocal imaging, and pulse-chase experiments showed that G196R and R468W mutations resulted in an absence of cell surface expression owing to endoplasmic reticulum (ER) retention. G196R and R468W mutants could be partially stabilized by low temperature. In blue native-polyacrylamide gel electrophoresis analysis, G196R and R468W mutants were either denatured or present in an aggregation complex. In contrast, S138F and R564C mutants were trafficked to the cell surface, but more rapidly degraded than WT protein. The c.228delC mutant did not affect endogenous NaPi uptake in OK cells. Thus, G196R and R468W mutations cause ER retention, while S138F and R564C mutations stimulate degradation of human NaPi-IIc in renal epithelial cells. Together, these data suggest that the NaPi-IIc mutants in HHRH show defective processing and stability.

scholarly journals Dileucine and YXXL Motifs in the Cytoplasmic Tail of the Bovine Leukemia Virus Transmembrane Envelope Protein Affect Protein Expression on the Cell Surface

2004 ◽  
Vol 78 (15) ◽  
pp. 8301-8311 ◽  
Author(s):  
Sinisa Novakovic ◽  
Earl T. Sawai ◽  
Kathryn Radke
Keyword(s):  
Cell Surface ◽  
Bovine Leukemia Virus ◽  
Leukemia Virus ◽  
Surface Display ◽  
Chimeric Protein ◽  
Surface Expression ◽  
Terminal Segment ◽  
Cell Surface Expression ◽  
Chimeric Proteins ◽  
Env Protein

ABSTRACT Several retroviruses downmodulate the cell surface expression of envelope (Env) proteins through peptide sequences located in the cytoplasmic tail of the transmembrane (TM) subunit. We investigated whether cell surface expression of a chimeric protein containing the cytoplasmic domain of the TM protein (CTM) of bovine leukemia virus (BLV) was regulated by two membrane-proximal dileucine motifs or by tyrosine Y487 or Y498 in YXXL motifs. A chimeric protein composed of the extracellular and membrane-spanning portions of human CD8-α plus a wild-type (wt) BLV CTM was detectable on the surface of only 40% of the cells in which it was transiently expressed. Replacement of either dileucine pair with alanines increased the level of surface display of chimeric proteins. Nearly all cells became surface positive when both dileucine motifs were altered simultaneously and when either an N-terminal segment containing both dileucine motifs or a C-terminal segment containing all YXXL motifs was deleted. In contrast, replacement of Y487 or Y498 with alanine or phenylalanine enabled only small increases in surface display compared with wt levels. Chimeric proteins had similar stabilities but were downmodulated from the cell surface at three different rates. Point mutants segregated into each of the three groups of proteins categorized according to these different rates. Interestingly, Y487 mutants were downmodulated less efficiently than Y498 mutants, which behaved like wt. CD8-CTM chimeric proteins were phosphorylated on serine residues, but the native BLV Env protein was not phosphorylated either in transfected cells or in a lymphoid cell line constitutively producing BLV. Thus, both dileucine and YXXL motifs within the BLV CTM contribute to downmodulation of a protein containing this domain. Interactions with other proteins may influence surface exposure of Env protein complexes in virus-infected cells, assisting in viral evasion of adaptive immunity.

scholarly journals Two-gene control of the expression of a murine Ia antigen.

1978 ◽  
Vol 148 (4) ◽  
pp. 925-939 ◽  
Author(s):  
P P Jones ◽  
D B Murphy ◽  
H O McDevitt
Keyword(s):  
Cell Surface ◽  
Polypeptide Chain ◽  
Polyacrylamide Gel Electrophoresis ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Gene Control ◽  
Cell Surface Molecules ◽  
Surface Molecules ◽  
Ia Antigens ◽  
Spleen Lymphocytes

Two dimensional polyacrylamide gel electrophoresis of Non-Idet P-40 extracts and of specific Ia immunoprecipitates from [35S]methionine-labeled mouse spleen lymphocytes has revealed that the cell surface expression of some Ia antigens appears to be controlled by two genes. One locus, which maps in the I-A subregion, is probably the structural gene for an Ia polypeptide chain. The second locus, which maps between the I-J and H-2D regions, controls whether this I-A encoded molecule (Ae) remains in the cytoplasm or is modified and expressed on the cell surface. Complementation between these two loci allowing surface expression of Ae can occur in the cis or trans chromosomal position. Both the I-A molecule and a polypeptide chain coded for by a locus in I-E are coprecipitated by anti-I-E antibodies, suggesting that these two chains are associated with each other as a multisubunit complex in the cell. Because the ability to complement I-A for Ae expression is a property only of those strains which synthesize an I-E-encoded protein, it is likely that the I-E product itself is regulating the expression of Ae. These observations suggest several mechanisms by which interaction between two I region loci can generate new cell surface molecules. As a result, they may have important implications for understanding the molecular basis of two gene control of immune responsiveness and immune suppression.

scholarly journals Cell Surface Expression of the Bovine Leukemia Virus-Binding Receptor on B and T Lymphocytes Is Induced by Receptor Engagement

2008 ◽  
Vol 181 (2) ◽  
pp. 891-898 ◽  
Author(s):  
Madakasira Lavanya ◽  
Sandrina Kinet ◽  
Amélie Montel-Hagen ◽  
Cédric Mongellaz ◽  
Jean-Luc Battini ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Cell Surface ◽  
Bovine Leukemia Virus ◽  
Leukemia Virus ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Virus Binding ◽  
B And T Lymphocytes

scholarly journals A transformation-associated 130-kD cell surface glycoprotein is growth controlled in normal human cells.

1988 ◽  
Vol 167 (5) ◽  
pp. 1684-1696 ◽  
Author(s):  
C E Klein ◽  
H L Ozer ◽  
F Traganos ◽  
J Atzpodien ◽  
H F Oettgen ◽  
...  
Keyword(s):  
Cell Surface ◽  
Surface Expression ◽  
Human Cells ◽  
Surface Glycoprotein ◽  
Cell Surface Expression ◽  
Quiescent State ◽  
Cell Surface Glycoprotein ◽  
Altered Expression ◽  
Serum Stimulation ◽  
Fetal Fibroblasts

Two characteristics of cell surface molecules involved in the regulation of cell proliferation are altered expression in relation to growth phase in normal cells and overexpression in transformed cells. Here, we describe a similar pattern of expression for a 130-kD cell surface glycoprotein (gp 130) in human cells. Synthesis and cell surface expression of gp130 were greatly increased in both virally and chemically transformed fibroblasts, fibrosarcomas, a squamous cell carcinoma of the skin, and T cell leukemia lines. Furthermore, gp130 expression was induced in serum-starved fetal fibroblasts by serum stimulation, and in fresh T cells by various activating agents. Expression in response to serum stimulation was associated primarily with the transition from a quiescent state (G0) into the cell cycle (G1).

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