Characterization of specific binding sites for [3H]-staurosporine on various protein kinases.
Binding of [3H]-staurosporine to different protein kinases was time-dependent, reversible and saturable. Scatchard analysis of saturation isotherms indicated one class of binding sites for [3H]-staurosporine with dissociation constants (KD) of 9.6, 2.0, 3.0 and 7.4 nM for protein kinase C, cAMP-dependent protein kinase, tyrosine protein kinase and calcium/calmodulin-dependent protein kinase respectively. [3H]-staurosporine binding was fully displaced by unlabelled staurosporine or the related compound K-252a whereas other protein kinase inhibitors (H-7, H-8 and W-7) did not compete with [3H]-staurosporine. These data confirm that sataurosporine shows no selectivity for different protein kinases and suggest the putative existence of distinct, specific binding sites for [3H]-staurosporine on these enzymes.
Herbert
J M
JM
Sanofi Recherche, Toulouse, France.
Seban
E
E
Maffrand
J P
JP
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000255:Adenosine Triphosphate / Q000378:metabolism; D000470:Alkaloids / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000201:enzymology; D002227:Carbazoles / Q000378:metabolism; D026121:Indole Alkaloids; D007546:Isoquinolines / Q000378:metabolism; D007700:Kinetics; D010879:Piperazines / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D019311:Staurosporine; D013449:Sulfonamides / Q000378:metabolism
D000470:Alkaloids; D002227:Carbazoles; D026121:Indole Alkaloids; D007546:Isoquinolines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; C017967:W 7; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C053177:N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide; D000255:Adenosine Triphosphate; C049985:staurosporine aglycone; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D019311:Staurosporine