Human CD38, a cell-surface protein with multiple functions.
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.
Mehta
K
K
Department of Bioimmunotherapy, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Shahid
U
U
Malavasi
F
F
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D002450:Cell Communication; D002462:Cell Membrane / Q000378:metabolism; D004798:Enzymes / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins; D009699:N-Glycosyl Hydrolases / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D014018:Tissue Distribution
D015703:Antigens, CD; D000943:Antigens, Differentiation; D004798:Enzymes; D008562:Membrane Glycoproteins; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1