Human CD38, a cell‐surface protein with multiple functions

Abstract

Human CD38 is a nonlineage-restricted type II transmembrane glycoprotein that has emerged as a multifunctional protein in recent years. It can serve as an ectoenzyme that catalyzes the synthesis and hydrolysis of cyclic ADP-ribose, a recently identified Ca2+ mobilizing agent that acts independently of inositol triphosphate. The enzymatic functions of CD38 probably contribute to an array of its immunoregulatory functions. The release of soluble CD38 and the ability of membrane-bound CD38 to become internalized in response to appropriate stimuli suggest that extracellular and intracellular roles for this protein are equally plausible. Ligation of CD38 with agonistic antibodies induces diverse effects in hematopoietic cells that range from growth stimulation to induction and prevention from apoptosis, induction of cytokines, activation of kinases, and phosphorylation of certain proteins. These observations suggest that CD38 may serve as receptor for an as yet unidentified ligand. Other molecules that share significant structural and functional homology to CD38 have been identified in humans and mice, suggesting that these molecules may represent a new family of proteins. Understanding the role of CD38 in certain pathological conditions such as myeloma, X-linked agammaglobulinemia, and HIV infection may provide insight into its physiological functions.

Highly purified CD38+ and CD38− sub-clones derived from the same chronic lymphocytic leukemia patient have distinct gene expression signatures despite their monoclonal origin

“…[9][10][11][12][13] Among these disparate roles, CD38 has been reported to be involved in lymphocyte activation and ligation of CD38 using a monoclonal antibody agonist has been shown to produce diverse responses including growth, differentiation and apoptosis. 14 Several groups have suggested that CD38 may be involved in signaling through the B-cell receptor (BCR) in CLL, [15][16][17] and in this regard we have recently shown an association between CD38 expression and the tyrosine kinase ZAP-70. 18 Furthermore, a recent study has shown an association between CD38 expression, activation marker expression and differential responses to interferon stimulation.…”

CD38 Signaling in T Cells Is Initiated within a Subset of Membrane Rafts Containing Lck and the CD3-ζ Subunit of the T Cell Antigen Receptor

“…0.5-ml fractions were collected, and aliquots of each fraction were analyzed by Western blot for the indicated proteins or ganglioside GM1. Densitometric data on rafts (fractions 2-4) and soluble (fractions [7][8] …”

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

“…K. Mehta (Houston, TX) suggested that the engagement of CD38 by CD31 plays a role in the retinoic acid syndrome (RAS), a life-threatening complication of ATRA therapy in acute myeloid leukemia. A significant proportion of patients given ATRA for acute promyelocytic or myeloblastic leukemia develop acute respiratory distress caused by massive pulmonary infiltration with newly differentiated granulocytes [30]. Normal granulocytes or dimethyl sulfoxide-treated leukemic cells are CD38 Ϫ but a single dose of ATRA induces strong CD38 expression in the leukemic cells [10], leading to the speculation that their interaction with CD31 on lung endothelium represents an important pathogenetic factor.…”