Mechanism-based small molecule probes for labeling CD38 on live cells.
CD38 is a type II transmembrane glycoprotein with multiple functions. It acts as an ecto-enzyme as well as a receptor. The enzymatic activity catalyzes the formation of two potent Ca(2+) releasing agents: cyclic adenosine diphosphate ribose (cADPR) from nicotinamide adenine dinucleotide (NAD) and nicotinic acid adenine dinucleotide phosphate (NAADP) from NAD phosphate (NADP). The receptor function of CD38 leads to the phosphorylation of intracellular signaling proteins and the up-regulation of cytokine production in immune cells. These two functions of CD38 underlie its involvement in various biological processes, such as hormone secretion, immune cell differentiation, and immune responses. Clinically, CD38 is used as a negative prognosis marker for chronic lymphatic leukemia (CLL). However, a clear molecular understanding of CD38's role in physiology and pathology is still lacking. To facilitate the study of CD38 at cellular and molecular levels, here we report a mechanism-based method for fluorescently labeling CD38 on live cells. This labeling method does not interfere with the receptor function of CD38 and the downstream signaling. The labeling method is thus a useful tool to study the receptor function of CD38 in live cells. In addition, since the mechanism-based labeling also inhibits the enzymatic activity of CD38, it should be useful for dissecting the receptor function of CD38 without interference from its enzyme function in complicated biological processes.
Jiang
Hong
H
Department of Chemistry and Chemical Biology, Cornell High Energy Synchrotron Source, Cornell University, Ithaca, New York 14853, USA.
Congleton
Johanna
J
Liu
Qun
Q
Merchant
Paolomi
P
Malavasi
Fabio
F
Lee
Hon Cheung
HC
Hao
Quan
Q
Yen
Andrew
A
Lin
Hening
H
D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry*; D018922:HL-60 Cells; D006801:Humans; D009537:Nicotinamide Mononucleotide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D012235:Rhodamines / Q000737:chemistry; D015398:Signal Transduction
D005456:Fluorescent Dyes; D012235:Rhodamines; D009537:Nicotinamide Mononucleotide; D051997:ADP-ribosyl Cyclase 1