Isoquinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide-dependent protein kinase and protein kinase C

Hidaka, Hiroyoshi; Inagaki, Masaki; Kawamoto, Sachiyo; Sasaki, Yasuharu

doi:10.1021/bi00316a032

Cited by 2,709 publications

(1,230 citation statements)

References 24 publications

Supporting

Mentioning

1,160

Contrasting

Unclassified

Order By: Relevance

“…0.1 mmol.l-1) or the protein kinase inhibitor H-9 (0-20 gmol.l-1). The drug H-9 has been shown to inhibit cGMP dependent protein kinase (Ki 0.87 pmol.l-1; Hidaka et al 1984). The proteineaous protein kinase inhibitor (Edelmann et al 1987) caused less than 50% inhibition at a final concentration of 40 gg inhibitor per ml.…”

Section: -1 In the Absence Of Mn 2 + Resulted In A Continualmentioning

confidence: 99%

A guanosine 5?-triphosphate-dependent protein kinase is localized in the outer envelope membrane of pea chloroplasts

Soll¹,

Fischer²,

Keegstra

1988

Planta

View full text Add to dashboard Cite

Abstract.A guanosine 5'-triphosphate (GTP)-dependent protein kinase was detected in preparations of outer chloroplast envelope membranes of pea (Pisum sativum L.) chloroplasts. The proteinkinase activity was capable of phosphorylating several envelope-membrane proteins. The major phosphorylated products were 23-and 32.5-kilodalton proteins of the outer envelope membrane. Several other envelope proteins were labeled to a lesser extent. Following acid hydrolysis of the labeled proteins, most of the label was detected as phosphoserine with only minor amounts detected as phosphothreonine. Several criteria were used to distinguish the GTP-dependent protein kinase from an ATP-dependent kinase also present in the outer envelope membrane. The ATP-dependent kinase phosphorylated a very different set of envelope-membrane proteins. Heparin inhibited the GTP-dependent kinase but had little effect upon the ATP-dependent enzyme. The GTP-dependent enzyme accepted phosvitin as an external protein substrate whereas the ATP-dependent enzyme did not. The outer membrane of the chloroplast envelope also contained a phosphotransferase capable of transferring labeled phosphate from [7-32p]GTP to ADP to yield (7-32p]ATP. Consequently, addition of ADP to a GTP-dependent protein-kinase assay resulted in a switch in the pattern of labeled products from that seen with GTP to that typically seen with ATP.

show abstract

Section: -1 In the Absence Of Mn 2 + Resulted In A Continualmentioning

confidence: 99%

A guanosine 5?-triphosphate-dependent protein kinase is localized in the outer envelope membrane of pea chloroplasts

Soll¹,

Fischer²,

Keegstra

1988

Planta

View full text Add to dashboard Cite

show abstract

“…In an attempt to investigate hypoxia-induced EPO mRNA accumulation in the presence of reduced activity of PKC, cells exposed to 3% oxygen for 2.5 h were treated with staurosporine [40], the staurosporine derivatives CGP 41251 [35], RO 318220, RO 317549 [9,12] and the isoquinolinesulphonamides H7, H8 and H9 [26]. In order to assess unspecific alterations of RNA synthesis, [3H]uridine incorporation was measured in parallel.…”

Section: Effects Of Kinase Inhibitors On Epo Mrna Levels and Total Rnmentioning

confidence: 99%

Hypoxia-induced accumulation of erythropoietin mRNA in isolated hepatocytes is inhibited by protein kinase C

et al. 1994

View full text Add to dashboard Cite

Abstract.To define the role of protein kinase C (PKC) in oxygen-dependent production of erythropoietin (EPO) in the liver, we have determined EPO messenger ribonucleic acid (mRNA) expression in primary cultures of juvenile rat hepatocytes incubated at different oxygen tensions in the absence and presence of phorbol esters, vasopressin, and structurally different kinase inhibitors. Upon reduction of oxygen concentrations from 40% to 3% EPO mRNA in cultured hepatocytes increased markedly within 1.25 h, reached maximal values after 2.5 h and remained elevated for up to 72 h. Treatment of hepatocytes during 1.25-5 h of hypoxic exposure with phorbol 12-myristate-13 acetate (PMA) attenuated hypoxiainduced EPO mRNA levels dose-dependently by a maximum of approximately 50%. This inhibitory effect of PMA disappeared upon treatment for more than 5 h and was completely lost after incubation for 9 and 18 h in the presence of 10 -6 M and 10 -7 M PMA, respectively. Phorbol 12,13-dibutyrate and vasopressin also inhibited EPO mRNA accumulation, whereas 4 alpha-phorbol 12,13-didecanoate was ineffective. Western blot analysis of PKC isozymes revealed the presence of PKC alpha, beta II, delta, epsilon and zeta and provided no evidence that the PMA-induced inhibition of EPO expression was associated with depletion of any of these isozymes. Conversely, PMA-induced inhibition of EPO mRNA accumulation was paralleled by translocation of PKC alpha from cytosol to membranes and the time-and dose-dependent attenuation of the inhibitory effect of PMA on EPO mRNA levels was paralleled by down-regulation of PKC alpha. A dose-dependent inhibition of EPO mRNA formation, independent of effects on total RNA synthesis, as determined by [3H]uridine incorporation, was also found in the presence of the kinase inhibitor staurosporine (EDso --2 • 10 s M) and three structurally related derivatives with increased selectivity for PKC (RO 317549, EDso --1 • -6 M; RO 318220, EDso --lX

show abstract

“…H-7, an isoquinolesulfonamide, is an active-site inhibitor of PKC [14]. In order to assess the significance of elevated PKC activity in the ADR resistance phenotypes of UV-2237M-rev and UV-2237M-ADR R cells, we tested the capacity of H-7 to reverse the resistance phenotype.…”

Section: Reversal Of the Adr Resistance Phenotype In Uv-2237m-rev Andmentioning

confidence: 99%

Level of protein kinase C activity correlates directly with resistance to adriamycin in murine fibrosarcoma cells

et al. 1989

View full text Add to dashboard Cite

In this report, we demonstrate a direct correlation between protein kinase C (PKC) activity and adriamycin (ADR) resistance in mouse fibrosarcoma cells. PKC activity was measured in four murine UV-2237M fibrosarcoma cell lines that differed in the degrees to which they expressed resistance to ADR, which is an inhibitor of PKC. A comparison of the four cell lines revealed a positive correlation between the level of PKC activity and resistance to ADR. Incubation of the cells with the PKC inhibitor H-7 produced a partial reversal of ADR resistance. Taken together, these results suggest a role for PKC in the mechanism of ADR resistance.

show abstract

Isoquinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide-dependent protein kinase and protein kinase C

Cited by 2,709 publications

References 24 publications

A guanosine 5?-triphosphate-dependent protein kinase is localized in the outer envelope membrane of pea chloroplasts

A guanosine 5?-triphosphate-dependent protein kinase is localized in the outer envelope membrane of pea chloroplasts

Hypoxia-induced accumulation of erythropoietin mRNA in isolated hepatocytes is inhibited by protein kinase C

Level of protein kinase C activity correlates directly with resistance to adriamycin in murine fibrosarcoma cells

Contact Info

Product

Resources

About