Tetrahydropterins interfere with the G protein pathway in Dictyostelium discoideum.
The cellular slime mold Dictyostelium discoideum produces tetrahydrodictyopterin, the D-threo-isomer of tetrahydrobiopterin. During cyclic AMP coordinated aggregation, the G protein linked signalling pathway is involved in the regulation of the initial enzyme GTP cyclohydrolase I [M. Gütlich et al., Biochem. J. 314, 95-101 (1996)]. We now find that cyclic AMP stimulated binding of GTPgammaS to the membrane fraction is inhibited by tetrahydrodictyopterin and tetrahydrobiopterin. Inhibition was a function of GTPgammaS concentration and the analysis of the kinetic data pointed to a competitive type of inhibition. The inhibition of G protein activation was accompanied by a loss of adenylyl cyclase activation. Because the GTPgammaS- and G protein-dependent reduction of receptor affinity for cyclic AMP was also attenuated, we conclude that tetrahydrodictyopterin and tetrahydrobiopterin interfere with activation of G proteins by inhibiting GDP-GTP exchange.
Ziegler
I
I
GSF-Institut für Klinische Molekularbiologie und Tumorgenetik, München, Germany.
Gütlich
M
M
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004023:Dictyostelium / Q000378:metabolism*; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000037:antagonists & inhibitors / Q000378:metabolism
D001708:Biopterins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; C003402:sapropterin