Inhibition of GTP-utilizing enzymes by tyrphostins.
Tyrphostins are a group of organic compounds which are widely used as a tool to specifically inhibit protein tyrosine kinases (Yaish, P., Gazit, A., Gilon, C., and levitzki A. (1988) Science 242, 933-935; Gazit, A., Yaish, P., Gilon, C., and Levitzki A. (1989) J. Med. Chem. 32, 2344-2352; Lyall, R. M., Zilberstein, A., Gazit, A., Gilon, C., Levitzki, A., and Schlessinger J. (1989) J. Biol. Chem. 264, 14503-14509; Osherov, N., Gazit, A., Gilon, C., and Levitzki, A. (1993) J. Biol. Chem. 268, 11134-11142). We report here that members of the tyrphostin family inhibit the GTPase activity of transducin and the enzymatic activities of other GTP-utilizing proteins in retinal rod outer segments, such as guanylyl cyclase or fructose-6-phosphate kinase. In contrast, ATP-utilizing enzymes such as hexokinase or rhodopsin kinase were not effected.
Wolbring
G
G
Department of Medical Biochemistry, University of Calgary, Alberta, Canada.
Hollenberg
M D
MD
Schnetkamp
P P
PP
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000818:Animals; D002396:Catechols / Q000494:pharmacology*; D002417:Cattle; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors*; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors*; D007700:Kinetics; D009570:Nitriles / Q000494:pharmacology*; D010732:Phosphofructokinase-1 / Q000037:antagonists & inhibitors*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D012374:Rod Cell Outer Segment / Q000201:enzymology; D015293:Transducin / Q000037:antagonists & inhibitors*; D020032:Tyrphostins
D002396:Catechols; D009570:Nitriles; D020032:Tyrphostins; C060152:tyrphostin 47; D006160:Guanosine Triphosphate; D010732:Phosphofructokinase-1; D011505:Protein-Tyrosine Kinases; D000251:Adenosine Triphosphatases; D020558:GTP Phosphohydrolases; D015293:Transducin; D006162:Guanylate Cyclase