INDUCTION OF NITRIC-OXIDE RELEASE BY MRC OX-44 (ANTI-CD53) THROUGH A PROTEIN-KINASE C-DEPENDENT PATHWAY IN RAT MACROPHAGES

Many membrane proteins are implicated in the control of cell function by triggering specific signaling pathways. There is a new family of me mbrane proteins, defined by its structural motifs, which includes seve ral lymphoid antigens, but lacks a function. To study its biological r ole, we determined which signaling pathways are affected by the CD53 a ntigen, a prototypic member of this family, in rat macrophages. Activa tion of CD53 by cross-linking results in an increase in inositol phosp hates and diacylglycerol and in Ca2+ mobilization, which are insensiti ve to pertussis or cholera toxins. There is a translocation of protein kinase C to the membrane accompanied by nitric oxide (NO) release in macrophages. This effect is the result of the expression of the induci ble nitric oxide synthase (iNOS), which is dependent on protein kinase C and protein synthesis. These results have linked a new receptor wit h a specific pathway of NO induction and thus have opened up a novel a spect of NO regulation in cell biology.