Cyclase

About: Cyclase is a research topic. Over the lifetime, 10162 publications have been published within this topic receiving 388566 citations.

CD38: a new paradigm in lymphocyte activation and signal transduction.

Abstract: CD38 is a type II transmembrane glycoprotein that is extensively expressed on cells of hematopoietic and non-hematopoietic lineage. Although the intracellular domain of CD38 is not homologous to any known proteins, the extracellular domain of CD38 is structurally related to enzymes in the ADP-ribosyl cyclase family. The structural homology between CD38 and the cyclase family members extends to functional homology, as the extracellular domain of CD38 can mediate the catalysis of beta-NAD+ into nicotinamide, ADP-ribose (ADPR) and, to a lesser extent, into cyclic ADPR-ribose (cADPR). Extensive investigation in other systems has shown that cADPR is an important regulator of intracellular Ca2+ release. Since engagement of CD38 on hematopoietic cells with anti-CD38 Abs has been shown to have potent effects on a number of in vitro cellular responses, we have speculated that cADPR might control CD38-mediated signal transduction. However, it has been difficult to understand how a mediator which is typically an intracellular signaling molecule could potentiate its effects from an extracellular location, thus posing a dilemma which pertains to all ecto-enzymes and the mechanisms by which they regulate signal transduction and cellular processes. This review describes the biologic properties of murine CD38, its role in humoral immunity, and its signal transduction properties in B lymphocytes. We suggest that signaling through CD38 represents a new paradigm in lymphocyte signal transduction and is predicated upon extracellular, rather than intracellular, crosstalk.

Prostacyclin increases cyclic AMP levels and adenylate cyclase activity in platelets

Abstract: PROSTACYCLIN (PGX) (ref. 1) is the name proposed for the metabolic product of a recently discovered enzymic transformation of the prostaglandin endoperoxides PGG2 and PGH2 (refs 2–4). Prostacyclin synthetase, the enzyme which catalyses this conversion, is particularly active in the microsomal fraction of blood vessel walls3,4 although there is evidence that it is also present in the rat stomach fundus3. The prostaglandin endoperoxides, PGG2 and PGH2, have been shown to contract arterial smooth muscle and to cause platelet aggregation5,6, whereas, in contrast, prostacyclin relaxes arterial strips and prevents platelets aggregation3. A biochemical interaction has therefore been postulated to exist between platelets and the blood vessels wall, such that endoperoxides derived from platelets are converted by the vessel wall into prostacylin, which in turn actively prevents the deposition of platelets on the vascular endothelium2,4. In general, agents which inhibit platelet aggregation, such as PGE1, increase cyclic AMP levels, whereas agents causing aggregation lower platelet cyclic AMP levels7. The ability of prostacyclin to rapidly reverse or prevent platelet aggregation suggested that its action on the platelet might, like that of PGE1, be mediated by an increase in cyclic AMP levels. This hypothesis is supported by the experiments detailed here which strongly suggest that prostacyclin generated by incubation of arachidonic acid, platelets and aortic tissue, causes a rapid and pronounced accumulation of cyclic AMP by intact platelets, as well as stimulation of adenylates cyclase in isolated platelet membranes.