Isolation and structural characterization of the human 4F2 heavy-chain gene, an inducible gene involved in T-lymphocyte activation.

Gottesdiener, Keith; Karpinski, Beverly A.; Lindsten, Tullia; Strominger, J L; Jones, N H; Thompson, Craig B.; Leiden, Jeffrey M.

doi:10.1128/mcb.8.9.3809

Cited by 66 publications

(64 citation statements)

References 26 publications

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“…Thus, the cellular BLV-binding receptor is representative of a new metabolic marker that characterizes an activated lymphocyte. In addition to Glut1, the nutrient receptors that have been found to be crucial for lymphocyte development and proliferation include the CD71 transferrin receptor which mediates iron uptake (54 -56) and CD98 (42F), a subunit of L-amino acid transporters (57)(58)(59). The identities of other nutrient receptors belonging to this group will undoubtedly be elucidated in the next few years and the BLV receptor promises to join this expanding list.…”

Section: Discussionmentioning

confidence: 99%

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

Lavanya

Kinet

Montel‐Hagen

et al. 2008

The Journal of Immunology

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Bovine leukemia virus (BLV), one of the most common infectious viruses of cattle, is endemic in many herds. Approximately 30–40% of adult cows in the United States are infected by this oncogenic C-type retrovirus and 1–5% of animals will eventually develop a malignant lymphoma. BLV, like the human and simian T cell leukemia viruses, is a deltaretrovirus but, in contrast with the latter, the BLV receptor remains unidentified. In this study, we demonstrate that the amino-terminal 182 residues of the BLV envelope glycoprotein surface unit encompasses the receptor-binding domain. A bona fide interaction of this receptor-binding domain with the BLV receptor was demonstrated by specific interference with BLV, but not human T cell leukemia virus, envelope glycoprotein-mediated binding. We generated a rabbit Ig Fc-tagged BLV receptor-binding domain construct and ascertained that the ligand binds the BLV receptor on target cells from multiple species. Using this tool, we determined that the BLV-binding receptor is expressed on differentiating pro/pre-B cells in mouse bone marrow. However, the receptor was not detected on mature/quiescent B cells but was induced upon B cell activation. Activation of human B and T lymphocytes also induced surface BLV-binding receptor expression and required de novo protein synthesis. Receptor levels were down-regulated as activated lymphocytes returned to quiescence. In the human thymus, BLV-binding receptor expression was specifically detected on thymocytes responding to the IL-7 cytokine. Thus, expression of the BLV-binding receptor is a marker of enhanced metabolic activity in B cells, T cells, and thymocytes.

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Section: Discussionmentioning

confidence: 99%

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

Lavanya

Kinet

Montel‐Hagen

et al. 2008

The Journal of Immunology

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“…Amino acid availability represents an additional regulatory step for protein translation. Signal transduction by mTOR promotes increased amino acid uptake by up-regulating and maintaining surface expression of amino acids transporters (Gottesdiener et al 1988). Amino acids can directly influence the rate of protein synthesis through stimulation of mTOR.…”

Section: Tumor Suppressors and Oncogenes Constitute Metabolic Signalimentioning

confidence: 99%

Tumor suppressors and cell metabolism: a recipe for cancer growth

Jones¹,

Thompson²

2009

Genes Dev.

912

804

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Growing tumors face two major metabolic challenges—how to meet the bioenergetic and biosynthetic demands of increased cell proliferation, and how to survive environmental fluctuations in external nutrient and oxygen availability when tumor growth outpaces the delivery capabilities of the existing vasculature. Cancer cells display dramatically altered metabolic circuitry that appears to directly result from the oncogenic mutations selected during the tumorigenic process. An emerging theme in cancer biology is that many of the genes that can initiate tumorigenesis are intricately linked to metabolic regulation. In turn, it appears that a number of well-established tumor suppressors play critical roles in suppressing growth and/or proliferation when intracellular supplies of essential metabolites become reduced. In this review, we consider the potential role of tumor suppressors as metabolic regulators.

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“…mTOR also directs the cell surface expression of a wide variety of nutrient transporters, including amino acid transporters, low-density lipoprotein receptor, and transferrin receptor, in response to Akt signaling (34). In T cells, surface expression of the amino acid transporter component 4F2 H chain (4F2hc) is induced by CD28 costimulation in a rapamycin-sensitive fashion (35). Thus, control of glucose transport is coordinated with import of other nutrients required for cell growth via Akt and mTOR signaling.…”

Section: Regulation Of Other Metabolic Pathwaysmentioning

confidence: 99%

Regulation of T Lymphocyte Metabolism

Frauwirth

Thompson

2004

The Journal of Immunology

320

191

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Upon stimulation, lymphocytes develop from small resting cells into highly proliferative and secretory cells. Although a great deal of study has focused on the genetic program induced by Ag receptor signals, lymphocytes must also regulate their metabolic function to meet the energetic demands of activation. In this review, we discuss the changes in cellular metabolism that accompany lymphocyte activation, with a particular emphasis on glucose metabolism, a major source of both energy and biosynthetic building blocks. We will also cover the signaling pathways that positively and negatively regulate these changes to maintain metabolic homeostasis in cells that are rapidly growing, dividing, and differentiating.

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Isolation and structural characterization of the human 4F2 heavy-chain gene, an inducible gene involved in T-lymphocyte activation.

Abstract: The human 4F2 cell surface antigen is a 120-kilodalton (kDa) disulfide-linked heterodimer which is composed of an 80-to 90-kDa glycosylated heavy chain (4F2HC) and a 35-to 40-kDa nonglycosylated light chain (4F2LC

Cited by 66 publications

References 26 publications

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

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

Tumor suppressors and cell metabolism: a recipe for cancer growth

Regulation of T Lymphocyte Metabolism

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