Characterization of receptor tyrosine-specific protein kinases by the use of inhibitors. Staurosporine is a 100-times more potent inhibitor of insulin receptor than IGF-I receptor.
The receptors for insulin and insulin-like growth factor (IGF)-I carry intrinsic tyrosine-specific protein kinases (TPK) in their cytoplasmic domains that show 84% homology. Our previous studies using tyrosine-containing synthetic polymers (Arch. Biochem. Biophys. 260, 416, 1988) revealed subtle differences between the two receptor TPKs. In the present study, low molecular weight kinase inhibitors were used to compare the two receptor TPKs purified from human placenta. Staurosporine was the most potent inhibitor of both receptor TPKs among the three inhibitors tested. It was 100 times more inhibitory to insulin receptor TPK (ED50 = 61nM) than IGF-I receptor TPK (ED50 = 6.2 microM). Apigenin and kaempferol showed approximately the same inhibitory potency toward both TPKs with a range of 10 approximately 1000 microM. Staurosporine is thus an excellent tool to biochemically characterize the two receptor TPKs as well as to selectively inhibit insulin-activated TPK in intact cells.
Fujita-Yamaguchi
Y
Y
Department of Molecular Genetics, Beckman Research Institute of the City of Hope, Duarte, California 91010.
Kathuria
S
S
D000255:Adenosine Triphosphate / Q000378:metabolism; D000470:Alkaloids / Q000494:pharmacology*; D001667:Binding, Competitive; D020843:Chamomile; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D044949:Kaempferols; D015394:Molecular Structure; D009822:Oils, Volatile / Q000494:pharmacology; D010766:Phosphorylation; D010920:Placenta / Q000201:enzymology; D010946:Plants, Medicinal; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011972:Receptor, Insulin / Q000378:metabolism*; D017451:Receptors, Somatomedin; D019311:Staurosporine
D000470:Alkaloids; D005419:Flavonoids; D044949:Kaempferols; D009822:Oils, Volatile; D017451:Receptors, Somatomedin; C006552:kaempferol; D000255:Adenosine Triphosphate; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D011493:Protein Kinase C; D019311:Staurosporine