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

Human CD38 is a 45-kDa type II membrane glycoprotein with an intricate patt ern of expression in leukocytes, although evidence is ac cumulating of its quite widespread expression in cells of nonvascular origin. CD38 is a membe r of a nascent eukaryotic gene family encoding cytosolic and membrane-bound enzymes whose substrate is NAD, a coenzyme ubiquitously distributed in nat ure, Functionally, CD38 is an eclectic molecule with the ability not only t o catalyze but also to signal, to mobilize calcium, and to adhere to itself , to hyaluronan, and to other Ligands. Interaction with CD38 on various leu kocyte subpopulations has profound though diverse consequences on their lif e-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.