Activation of G-proteins by receptor-stimulated nucleoside diphosphate kinase in Dictyostelium.
Recently, interest in the enzyme nucleoside diphosphate kinase (EC2.7.4.6) has increased as a result of its possible involvement in cell proliferation and development. Since NDP kinase is one of the major sources of GTP in cells, it has been suggested that the effects of an altered NDP kinase activity on cellular processes might be the result of altered transmembrane signal transduction via guanine nucleotide-binding proteins (G-proteins). In the cellular slime mould Dictyostelium discoideum, extracellular cAMP induces an increase of phospholipase C activity via a surface cAMP receptor and G-proteins. In this paper it is demonstrated that part of the cellular NDP kinase is associated with the membrane and stimulated by cell surface cAMP receptors. The GTP produced by the action of NDP kinase is capable of activating G-proteins as monitored by altered G-protein-receptor interaction and the activation of the effector enzyme phospholipase C. Furthermore, specific monoclonal antibodies inhibit the effect of NDP kinase on G-protein activation. These results suggest that receptor-stimulated NDP kinase contributes to the mediation of hormone action by producing GTP for the activation of GTP-binding proteins.
Department of Biochemistry, University of Groningen, The Netherlands.
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Bominaar
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Molijn
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Pestel
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Veron
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PJ
Van Haastert
D000818:Animals; D000911:Antibodies, Monoclonal; D002462:Cell Membrane / Q000201:enzymology; D000242:Cyclic AMP / Q000378:metabolism; D004023:Dictyostelium / Q000201:enzymology*; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D009701:Nucleoside-Diphosphate Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011953:Receptors, Cyclic AMP / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D011953:Receptors, Cyclic AMP; D006153:Guanosine Diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D000242:Cyclic AMP; D009701:Nucleoside-Diphosphate Kinase; D019204:GTP-Binding Proteins