Abstract
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.
MeSH terms
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
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Adenosine Triphosphate / metabolism
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Alkaloids / metabolism*
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Animals
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Binding Sites
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Binding, Competitive
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Brain / enzymology
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Carbazoles / metabolism
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Indole Alkaloids
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Isoquinolines / metabolism
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Kinetics
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Piperazines / metabolism
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Protein Kinase C / antagonists & inhibitors
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Protein Kinase C / metabolism
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Protein Kinase Inhibitors
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Protein Kinases / metabolism*
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Protein-Tyrosine Kinases / metabolism
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Rats
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Staurosporine
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Sulfonamides / metabolism
Substances
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Alkaloids
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Carbazoles
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Indole Alkaloids
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Isoquinolines
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Piperazines
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Protein Kinase Inhibitors
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Sulfonamides
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W 7
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
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N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide
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Adenosine Triphosphate
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staurosporine aglycone
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Protein Kinases
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Protein-Tyrosine Kinases
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Protein Kinase C
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Staurosporine