Biochemical studies of the human thymocyte cell-surface antigens T6, T9 and T10

Terhorst, Cox; Agthoven, André Van; LeClair, Kenneth; Snow, Peter M.; Reinherz, Ellis L.; Schlossman, Stuart F.

doi:10.1016/0092-8674(81)90441-4

Cited by 258 publications

(75 citation statements)

References 35 publications

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“…1). The standard form or membrane monomer is a single chain with a M r ϭ 45,000 [2,3] and removal of N-linked carbohydrates by endoglycosidase-H treatment reduces the M r to 36,000 [3]. This is close to the predicted size of the CD38 polypeptide deduced from the amino acid sequence (M r ϭ 34,301) reported by D. Jackson and J.…”

Section: Structure Of Human Cd38 and Related Proteinssupporting

confidence: 58%

The metamorphosis of a molecule: from soluble enzyme to the leukocyte receptor CD38

Ferrero

Malavasi

1999

Journal of Leukocyte Biology

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Human CD38 is a 45-kDa type II membrane glycoprotein with an intricate pattern of expression in leukocytes, although evidence is accumulating of its quite widespread expression in cells of nonvascular origin. CD38 is a member of a nascent eukaryotic gene family encoding cytosolic and membrane-bound enzymes whose substrate is NAD, a coenzyme ubiquitously distributed in nature. Functionally, CD38 is an eclectic molecule with the ability not only to catalyze but also to signal, to mobilize calcium, and to adhere to itself, to hyaluronan, and to other ligands. Interaction with CD38 on various leukocyte subpopulations has profound though diverse consequences on their life-span, but these effects seem to be independent of the enzymatic activity of the molecule. CD38 challenges our expectations of a surface molecule and we must sift through its many guises to unmask its true nature. J. Leukoc. Biol. 65: 151-161; 1999.

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Section: Structure Of Human Cd38 and Related Proteinssupporting

confidence: 58%

The metamorphosis of a molecule: from soluble enzyme to the leukocyte receptor CD38

Ferrero

Malavasi

1999

Journal of Leukocyte Biology

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“…In a previous paper, we have shown that CD38 ligation 1 The abbreviations used are: mAb, monoclonal antibody; TCR, T cell antigen receptor; PLC-␥1, phospholipase C-␥1; ZAP-70, -associated protein-70; MAP, mitogen-activated protein; Erk, extracellular signalregulated protein kinase; MEK, MAP kinase or Erk kinase, also known as MAP kinase kinase; PTK, protein-tyrosine kinase; ITAM, immunoreceptor tyrosine-based activation motif; JK, Jurkat; PAGE, polyacrylamide gel electrophoresis; PVDF, polyvinylidene difluoride; ECL, enhanced chemiluminescence; HRP, horseradish peroxidase; PdBu, 4␣results in activation of at least two PTK-controlled signaling pathways, the CD3-/ZAP-70/PLC-␥1-dependent cascade and the Raf-1/MAP kinase pathway, suggesting a functional relationship between signals delivered through CD38 and the TCR (21). This assumption was strengthened by our finding that, in Jurkat T cells, CD38-mediated signaling events as increases in [Ca 2ϩ ] i or CD69 expression require the presence of the TCR/ CD3 (22).…”

mentioning

confidence: 99%

“…Human CD38 antigen is a 45-kDa type II transmembrane glycoprotein with a short N-terminal cytoplasmic domain and a long C-terminal extracellular domain (1,2). It is widely expressed in different cell types including thymocytes, activated T cells, and terminally differentiated B cells (plasma cells) (3).…”

mentioning

confidence: 99%

The CD3-γδε Transducing Module Mediates CD38-induced Protein-tyrosine Kinase and Mitogen-activated Protein Kinase Activation in Jurkat T Cells

Zubiaur

Guirado

Terhorst

et al. 1999

Journal of Biological Chemistry

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We have examined the ability of the CD3-␥␦⑀ and CD3-signaling modules of the T cell receptor (TCR) to couple CD38 to intracellular signaling pathways. The results demonstrated that in TCR ؉ T cells that express the whole set of CD3 subunits CD38 ligation led to complete tyrosine phosphorylation of both CD3-and CD3-⑀ polypeptide chains. In contrast, in TCR ؉ cells with a defective CD3-association CD38 engagement caused tyrosine phosphorylation of CD3-⑀ but not of CD3-. Despite these differences, in both cell types CD38 ligation resulted in protein-tyrosine kinase and mitogen-activated protein kinase activation. However, in cells expressing chimerical CD25-or CD25-⑀ receptors or in a TCR-␤ ؊ Jurkat T cell line, CD38 ligation did not result in tyrosine phosphorylation of the chimeric receptors, or CD3 subunits, or protein-tyrosine kinase or mitogenactivated protein kinase activation. In summary, these results support a model in which CD38 transduces activating signals inside the cell by means of CD3-⑀ and CD3-tyrosine phosphorylation. Moreover, these data identify the CD3-␥␦⑀ signaling module as a necessary and sufficient component of the TCR/CD3 complex involved in T cell activation through CD38.

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“…One function initially attributed to CD38 is the regulation of activation and proliferation of human T lymphocytes (6,7). CD38 ligation by agonistic mAbs induces rapid Ca 2+ fluxes and triggers the phosphorylation of a cascade of intracellular substrates, leading to activation of the NF-κB complex (8,9).…”

Section: Cd38 As a Surface Moleculementioning

confidence: 99%

Anti-CD38 Antibody Therapy: Windows of Opportunity Yielded by the Functional Characteristics of the Target Molecule

Chillemi

Zaccarello

Quarona

et al. 2013

Mol Med

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In vivo use of monoclonal antibodies (mAbs) has become a mainstay of routine clinical practice in the treatment of various human diseases. A number of molecules can serve as targets, according to the condition being treated. Now entering human clinical trials, CD38 molecule is a particularly attractive target because of its peculiar pattern of expression and its twin role as receptor and ectoenzyme. This review provides a range of analytical perspectives on the current progress in and challenges to anti-CD38 mAb therapy. We present a synopsis of the evidence available on CD38, particularly in myeloma and chronic lymphocytic leukemia (CLL). Our aim is to make the data from basic science helpful and accessible to a diverse clinical audience and, at the same time, to improve its potential for in vivo use. The topics covered include tissue distribution and signal implementation by mAb ligation and the possibility of increasing cell density on target cells by exploiting information about the molecule’s regulation in combination with drugs approved for in vivo use. Also analyzed is the behavior of CD38 as an enzyme: CD38 is a component of a pathway leading to the production of adenosine in the tumor microenvironment, thus inducing local anergy. Consequently, not only might CD38 be a prime target for mAb-mediated therapy, but its functional block may contribute to general improvement in cancer immunotherapy and outcomes.

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Biochemical studies of the human thymocyte cell-surface antigens T6, T9 and T10

Cited by 258 publications

References 35 publications

The metamorphosis of a molecule: from soluble enzyme to the leukocyte receptor CD38

The metamorphosis of a molecule: from soluble enzyme to the leukocyte receptor CD38

The CD3-γδε Transducing Module Mediates CD38-induced Protein-tyrosine Kinase and Mitogen-activated Protein Kinase Activation in Jurkat T Cells

Anti-CD38 Antibody Therapy: Windows of Opportunity Yielded by the Functional Characteristics of the Target Molecule

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