The OX-44 molecule couples to signaling pathways and is associated with CD2 on rat T lymphocytes and a natural killer cell line.

Bell, Gregory; Seaman, William E.; Niemi, Eréne C.; Imboden, John B.

doi:10.1084/jem.175.2.527

Cited by 71 publications

(45 citation statements)

References 37 publications

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“…5). CD53 has been implicated in mediating CD2 signaling pathways and thus is involved in immune responses (1). Moreover, patients with genetic CD53 deficiency show increased susceptibility to viral infections (29), suggesting that HIV-1 might interfere with this potentially antiviral pathway.…”

Section: Discussionmentioning

confidence: 99%

Cellular Gene Expression upon Human Immunodeficiency Virus Type 1 Infection of CD4⁺-T-Cell Lines

Wout

Lehrman

Mikheeva

et al. 2003

J Virol

173

123

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The expression levels of ϳ4,600 cellular RNA transcripts were assessed in CD4؉ -T-cell lines at different times after infection with human immunodeficiency virus type 1 strain BRU (HIV-1 BRU ) using DNA microarrays. We found that several classes of genes were inhibited by HIV-1 BRU infection, consistent with the G 2 arrest of HIV-1-infected cells induced by Vpr. These included genes involved in cell division and transcription, a family of DEAD-box proteins (RNA helicases), and all genes involved in translation and splicing. However, the overall level of cell activation and signaling was increased in infected cells, consistent with strong virus production. These included a subgroup of transcription factors, including EGR1 and JUN, suggesting they play a specific role in the HIV-1 life cycle. Some regulatory changes were cell line specific; however, the majority, including enzymes involved in cholesterol biosynthesis, of changes were regulated in most infected cell lines. Compendium analysis comparing gene expression profiles of our HIV-1 infection experiments to those of cells exposed to heat shock, interferon, or influenza A virus indicated that HIV-1 infection largely induced specific changes rather than simply activating stress response or cytokine response pathways. Thus, microarray analysis confirmed several known HIV-1 host cell interactions and permitted identification of specific cellular pathways not previously implicated in HIV-1 infection. Continuing analyses are expected to suggest strategies for impacting HIV-1 replication in vivo by targeting these pathways.

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Section: Discussionmentioning

confidence: 99%

Cellular Gene Expression upon Human Immunodeficiency Virus Type 1 Infection of CD4⁺-T-Cell Lines

Wout

Lehrman

Mikheeva

et al. 2003

J Virol

173

123

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“…RNK-16 cells that had been adapted for in vitro growth were passaged as described previously (5). Nylon wool nonadherent mononuclear cells (T cells) were isolated from the spleens of Fischer 344 rats as described previously (5).…”

Section: Methodsmentioning

confidence: 99%

“…T 8% polyacrylamide gels. Surface labelling of both T cells and T lymphoblasts by the lactoperoxidase method was performed as described previously (5).…”

Section: Methodsmentioning

confidence: 99%

Association of Src-like protein tyrosine kinases with the CD2 cell surface molecule in rat T lymphocytes and natural killer cells.

Bell¹,

Bolen²,

Imboden³

1992

Mol. Cell. Biol.

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The cell surface molecule CD2 has a signaling role in the activation of T lymphocytes and natural killer cells. Because perturbation of CD2 leads to the appearance of tyrosine-phosphorylated proteins, we investigated the possibility that CD2 associates with cytoplasmic protein tyrosine kinases. As determined by in vitro kinase assays and phosphoamino acid analysis, protein tyrosine kinase activity coprecipitated with CD2 from rat T lymphocytes, T lymphoblasts, thymocytes, interleukin-2-activated natural killer cells, and RNK-16 cells (a rat natural killer cell line). In each case, both p56kk and p590' were identified in the CD2 immunoprecipitate. In the thymus, the association between CD2 and these kinases occurred predominately in a small subset of thymocytes that had the cell surface phenotype of mature T cells, indicating that the association is a regulated event and occurs late in T-cell ontogeny. The finding that CD2 is associated with p56kk and p590f in detergent lysates suggests that interactions with these Src-like protein kinases play a critical role in CD2-mediated signal transduction.CD2, a 55-kDa cell surface glycoprotein, has both adhesion and signaling functions in the activation of T lymphocytes and natural killer (NK) cells (18,30,31). Perturbation of CD2 by the combination of its natural ligand (LFA-3) and certain monoclonal antibodies (MAbs) provides a potent stimulus for T-cell activation, triggering proliferative responses comparable to those elicited by either mitogenic lectins or MAbs to the T-cell receptor (TCR)-CD3 complex (18,31). CD2 also has the capacity to activate NK cells, as evidenced by the ability of CD2 MAbs to stimulate lysis of NK cell-resistant targets (30).The mechanism by which CD2 couples to signal transduction pathways is uncertain. As with the TCR-CD3 complex, appropriate stimulation of CD2 induces tyrosine phosphorylations and stimulates phosphatidylinositol turnover (3,17,20,23). These CD2-induced signaling responses depend on the cytoplasmic domain of CD2, which is relatively large (117 amino acids) and highly conserved among humans, rats, and mice (10,16,(26)(27)(28)38). CD2-mediated signaling also requires coexpression of molecules that are restricted in their tissue expression (2, 13, 16). CD2, for example, does not signal when it is expressed in fibroblasts by gene transfer (13, 16). One apparent requirement for CD2-mediated signaling is the coexpression of receptors that contain members of the CD3 (-chain family (19). Thus, CD2 cannot signal in T-cell mutants that lack TCR-CD3 but is functional in NK cells, which express ; in association with CD16, and signals when transfected into mast cells, which express the c-related y chain in association with the FcE receptor (1,4,6,19,35). The molecular basis by which (-chain expression permits CD2 to signal remains uncertain.Recent studies of lymphocyte activation have focused on the role played by the Src-like protein tyrosine kinases (PTKs) in coupling cell surface receptors to signaling path-* Corresponding author.ways...

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“…They are characterized by short intracellular amino and C termini without any predictable signaling function. Nevertheless, tetraspanins have been linked to the regulation of cell proliferation (1,2), cell adhesion and migration (3), human T cell leukemia virus (HTLV-1) 4 -induced syncytium formation (4), and cell signaling (5). Some tetraspanins such as CD81 are nearly ubiquitously expressed in the body.…”

mentioning

confidence: 99%

Release and Intercellular Transfer of Cell Surface CD81 Via Microparticles

Fritzsching¹,

Schwer²,

Kartenbeck

et al. 2002

The Journal of Immunology

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The human tetraspan molecule CD81 is a coreceptor in B and T cell activation and a candidate receptor for hepatitis C virus infection. We examined the surface expression of CD81 on B and T lymphocytes by quantitative flow cytometry. Upon cellular activation, CD81 surface levels were rapidly reduced. This reduction occurred as early as 1 h after activation and was linked to the release of CD81-positive microparticles into the cell culture medium. CD81 mRNA levels were not affected early after activation, but the release of CD81-positive microparticles was rapidly enhanced. In addition, intercellular transfer of CD81 was observed upon coculture of CD81-positive donor cells (Jurkat T cell line) with CD81-negative acceptor cells (U937 promonocytic cell line). This transfer was rapidly increased upon T cell activation, coinciding with enhanced CD81 release from activated Jurkat cells. We propose that the release and intercellular trafficking of CD81-positive microparticles regulate the expression of CD81 surface receptors in lymphocytes and play a role in the immune response during infections.

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The OX-44 molecule couples to signaling pathways and is associated with CD2 on rat T lymphocytes and a natural killer cell line.

Cited by 71 publications

References 37 publications

Cellular Gene Expression upon Human Immunodeficiency Virus Type 1 Infection of CD4⁺-T-Cell Lines

Cellular Gene Expression upon Human Immunodeficiency Virus Type 1 Infection of CD4⁺-T-Cell Lines

Association of Src-like protein tyrosine kinases with the CD2 cell surface molecule in rat T lymphocytes and natural killer cells.

Release and Intercellular Transfer of Cell Surface CD81 Via Microparticles

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The OX-44 molecule couples to signaling pathways and is associated with CD2 on rat T lymphocytes and a natural killer cell line.

Cited by 71 publications

References 37 publications

Cellular Gene Expression upon Human Immunodeficiency Virus Type 1 Infection of CD4+-T-Cell Lines

Cellular Gene Expression upon Human Immunodeficiency Virus Type 1 Infection of CD4+-T-Cell Lines

Association of Src-like protein tyrosine kinases with the CD2 cell surface molecule in rat T lymphocytes and natural killer cells.

Release and Intercellular Transfer of Cell Surface CD81 Via Microparticles

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Cellular Gene Expression upon Human Immunodeficiency Virus Type 1 Infection of CD4⁺-T-Cell Lines

Cellular Gene Expression upon Human Immunodeficiency Virus Type 1 Infection of CD4⁺-T-Cell Lines