Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Journal of Biological Chemistry |
| Vol/bind | 281 |
| Udgave nummer | 19 |
| Sider (fra-til) | 13199-208 |
| Antal sider | 9 |
| ISSN | 0021-9258 |
| DOI | |
| Status | Udgivet - 2006 |
Bibliografisk note
Keywords: Animals; COS Cells; Cercopithecus aethiops; GTP-Binding Proteins; Gene Expression Regulation; Humans; Killer Cells, Natural; Lymphocytes; Monocytes; Protein Isoforms; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Signal TransductionAdgang til dokumentet
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Molecular pharmacological phenotyping of EBI2. An orphan seven-transmembrane receptor with constitutive activity. / Rosenkilde, Mette M; Benned-Jensen, Tau; Holst, Peter J; Kledal, Thomas N; Lüttichau, Hans R; Larsen, Jørgen K; Christensen, Jan P; Schwartz, Thue W; Andersen, Helene.
I: Journal of Biological Chemistry, Bind 281, Nr. 19, 2006, s. 13199-208.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - Molecular pharmacological phenotyping of EBI2. An orphan seven-transmembrane receptor with constitutive activity
AU - Rosenkilde, Mette M
AU - Benned-Jensen, Tau
AU - Holst, Peter J
AU - Kledal, Thomas N
AU - Lüttichau, Hans R
AU - Larsen, Jørgen K
AU - Christensen, Jan P
AU - Schwartz, Thue W
AU - Andersen, Helene
N1 - Keywords: Animals; COS Cells; Cercopithecus aethiops; GTP-Binding Proteins; Gene Expression Regulation; Humans; Killer Cells, Natural; Lymphocytes; Monocytes; Protein Isoforms; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Signal Transduction
PY - 2006
Y1 - 2006
N2 - Epstein-Barr virus (EBV)-induced receptor 2 (EBI2) is an orphan seven-transmembrane (7TM) receptor originally identified as the most up-regulated gene (>200-fold) in EBV-infected cells. Here we show that EBI2 signals with constitutive activity through Galpha(i) as determined by a receptor-mediated inhibition of forskolin-induced cAMP production and an induction of the serum response element-driven transcriptional activity in a pertussis toxin-sensitive manner. Galpha(s) and Galpha(q) were not activated constitutively as determined by the lack of cAMP production, the lack of inositol phosphate turnover, and the lack of activities of the transcription factors: cAMP response element-binding protein and nuclear factor-kappaB. Immunohistochemistry and confocal microscopy of FLAG- and green fluorescent protein-tagged EBI2 revealed cell-surface expression. A putative N-terminal truncated version of EBI2, delta4-EBI2, showed similar expression and signaling through Galpha(i) as full-length EBI2. By using a 32P-labeled EBI2 probe we found a very high expression in lymphoid tissue (spleen and lymph node) and peripheral blood mononuclear cells and a high expression in lung tissue. Real-time PCR of EBV-infected cells showed high expression of EBI2 during latent and lytic infection, in contrast to the EBV-encoded 7TM receptor BILF1, which was induced during lytic infection. EBI2 clustered with the orphan GPR18 by alignment analysis as well as by close proximity in the chromosomal region 13q32.3. Based on the constitutive signaling and cellular expression pattern of EBI2, it is suggested that it may function in conjunction with BILF1 in the reprogramming of the cell during EBV infection.
AB - Epstein-Barr virus (EBV)-induced receptor 2 (EBI2) is an orphan seven-transmembrane (7TM) receptor originally identified as the most up-regulated gene (>200-fold) in EBV-infected cells. Here we show that EBI2 signals with constitutive activity through Galpha(i) as determined by a receptor-mediated inhibition of forskolin-induced cAMP production and an induction of the serum response element-driven transcriptional activity in a pertussis toxin-sensitive manner. Galpha(s) and Galpha(q) were not activated constitutively as determined by the lack of cAMP production, the lack of inositol phosphate turnover, and the lack of activities of the transcription factors: cAMP response element-binding protein and nuclear factor-kappaB. Immunohistochemistry and confocal microscopy of FLAG- and green fluorescent protein-tagged EBI2 revealed cell-surface expression. A putative N-terminal truncated version of EBI2, delta4-EBI2, showed similar expression and signaling through Galpha(i) as full-length EBI2. By using a 32P-labeled EBI2 probe we found a very high expression in lymphoid tissue (spleen and lymph node) and peripheral blood mononuclear cells and a high expression in lung tissue. Real-time PCR of EBV-infected cells showed high expression of EBI2 during latent and lytic infection, in contrast to the EBV-encoded 7TM receptor BILF1, which was induced during lytic infection. EBI2 clustered with the orphan GPR18 by alignment analysis as well as by close proximity in the chromosomal region 13q32.3. Based on the constitutive signaling and cellular expression pattern of EBI2, it is suggested that it may function in conjunction with BILF1 in the reprogramming of the cell during EBV infection.
U2 - 10.1074/jbc.M602245200
DO - 10.1074/jbc.M602245200
M3 - Journal article
C2 - 16540462
VL - 281
SP - 13199
EP - 13208
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 19
ER -