ACTIVATION OF G-PROTEINS BY RECEPTOR-STIMULATED NUCLEOSIDE DIPHOSPHATE KINASE IN DICTYOSTELIUM

Recently, interest in the enzyme nucleoside diphosphate kinase (EC 2.7 .4.6) has increased as a result of its possible involvement in cell pr oliferation and development. Since NDP kinase is one of the major sour ces of GTP in cells, it has been suggested that the effects of an alte red NDP kinase activity on cellular processes might be the result of a ltered transmembrane signal transduction via guanine nucleotide-bindin g proteins (G-proteins). In the cellular slime mould Dictyostelium dis coideum, extracellular cAMP induces an increase of phospholipase C act ivity via a surface cAMP receptor and G-proteins. In this paper it is demonstrated that part of the cellular NDP kinase is associated with t he membrane and stimulated by cell surface cAMP receptors. The GTP pro duced by the action of NDP kinase is capable of activating G-proteins as monitored by altered G-protein-receptor interaction and the activat ion of the effector enzyme phospholipase C. Furthermore, specific mono clonal antibodies inhibit the effect of NDP kinase on G-protein activa tion. These results suggest that receptor-stimulated NDP kinase contri butes to the mediation of hormone action by producing GTP for the acti vation of GTP-binding proteins.