Retinoid-mediated signaling pathways in CD38 antigen expression in myeloid leukemia cells.
The lymphocyte cell surface antigen CD38, which was originally described as a differentiation marker, has emerged as an important multifunctional protein. Its most intriguing and well characterized function is its ability to catalyze the synthesis of cyclic ADP-ribose (cADPR) from NAD. cADPR serves as an important second messenger in controlling the release of intracellular calcium from ryanodine-sensitive intracellular pools. By virtue of its ability to synthesize cADPR as well as to act as an adhesion and signal transduction molecule, CD38 may play a role in such diverse physiological processes as cell growth, apoptosis, differentiation, and inflammation. Equally interesting is the pattern of CD38 expression in hematopoietic cells. In the bone marrow, early precursor cells predominantly express CD38 antigen, whereas mature circulating blood cells lack or express very low levels. The expression is also high on malignant hematopoietic cells and thus may be of prognostic relevance in certain leukemias. Presently, there is little information available on the factors that regulate the expression of CD38 antigen in hematopoietic cells. In this review, we summarize recent findings on the regulation of CD38 antigen by retinoids (vitamin A and related compounds). At least in the myeloid cell lineage, retinoids appear to be exquisitely potent and specific inducers of CD38 antigen expression, and retinoid-induced expression of CD38 is mediated via activation of the retinoic acid-alpha (RAR alpha) nuclear receptor.
Department of Bioimmunotherapy, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA. kmehta@mdacc.tmc.edu
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D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000096:biosynthesis*; D006801:Humans; D007951:Leukemia, Myeloid / Q000276:immunology* / Q000378:metabolism*; D008562:Membrane Glycoproteins; D009244:NAD+ Nucleosidase / Q000096:biosynthesis*; D012176:Retinoids / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D008562:Membrane Glycoproteins; D012176:Retinoids; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1