Effect of protein kinase inhibitors on protein phosphorylation and germination of aerial spores fromStreptomyces coelicolor

2007 ◽  
Vol 52 (3) ◽  
pp. 215-222 ◽  
Author(s):  
P. Palečková ◽  
F. Kontrová ◽  
O. Kofroňová ◽  
J. Bobek ◽  
O. Benada ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Phosphorylation ◽  
Kinase Inhibitors ◽  
Protein Kinase Inhibitors

scholarly journals Inhibitors of human cytomegalovirus replication drastically reduce the activity of the viral protein kinase pUL97

2001 ◽  
Vol 82 (6) ◽  
pp. 1439-1450 ◽  
Author(s):  
Manfred Marschall ◽  
Matthias Stein-Gerlach ◽  
Martina Freitag ◽  
Regina Kupfer ◽  
Miriam van den Bogaard ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Phosphorylation ◽  
Human Cytomegalovirus ◽  
Viral Protein ◽  
Kinase Activity ◽  
Kinase Inhibitors ◽  
Critical Role ◽  
Protein Kinase Inhibitors ◽  
Viral Protein Kinase ◽  
Exact Function

The UL97-encoded protein kinase (pUL97) of human cytomegalovirus (HCMV) plays a critical role in the control of virus replication. Deletion of the UL97 gene results in a drastic reduction in the replication efficiency. Although the exact function of pUL97 remains unclear and its sensitivity to specific inhibitors is speculative, protein kinase inhibitors of the indolocarbazole class are effective inhibitors of cytomegalovirus. Based on the phosphorylation of ganciclovir (GCV), a novel quantification system for pUL97 kinase activity was established: the phosphorylated form of GCV exerts an easily quantifiable cytotoxic effect in transfected cells. Importantly, the addition of indolocarbazole compounds, Gö6976 and NGIC-I, which were highly effective at nanomolar concentrations while other protein kinase inhibitors were not, led to a significant reduction of pUL97 kinase activity. It was also demonstrated that a catalytically inactive mutant of pUL97, K355M, and a GCV-resistant mutant, M460I, were both negative for GCV phosphorylation, although protein phosphorylation remained detectable for the latter mutant. In vitro kinase assays were used to confirm the levels of pUL97-mediated phosphorylation recorded. To generate a tool for screening large numbers of putative inhibitors that preferentially interfere with GCV as well as protein phosphorylation, pUL97-expressing cell clones with stable pUL97 kinase activity were selected. This study demonstrates that certain indolocarbazole compounds are potent pUL97 inhibitors and, therefore, represent novel candidates for antiviral drugs that target viral protein kinase functions.

scholarly journals Regulation of transferrin receptor recycling by protein phosphorylation

1994 ◽  
Vol 303 (2) ◽  
pp. 647-655 ◽  
Author(s):  
J R Beauchamp ◽  
P G Woodman
Keyword(s):  
Protein Kinase ◽  
Protein Phosphorylation ◽  
Cell Lines ◽  
Okadaic Acid ◽  
Transferrin Receptor ◽  
Kinase Inhibitors ◽  
K562 Cells ◽  
Protein Kinase Inhibitors ◽  
Endocytic Pathway ◽  
Transferrin Uptake

The effect of the protein phosphatase inhibitor okadaic acid on transferrin receptor internalization and recycling was examined in HeLa and K562 cells. Okadaic acid inhibited receptor uptake by more than 85% in both cell lines, whereas it affected transferrin recycling to differing degrees: recycling in HeLa cells was inhibited by greater than 90%, compared with only 65% in K562 cells. Okadaic acid also caused a marked redistribution of receptors in each cell line, which was accounted for by the difference in the extent to which transferrin uptake and recycling were inhibited. These effects were most likely mediated by a protein kinase, as they were delayed by 10-15 min and could be suppressed by prior incubation with certain protein kinase inhibitors. In addition, it was found that specific kinase inhibitors affected basal rates of transferrin uptake and recycling, although the extent of these effects differed between cell lines. Together, these results suggest that a complex pattern of protein phosphorylation influences the flux of the endocytic pathway in interphase cells.

scholarly journals Thiazolidine-diones. Biochemical and biological activity of a novel class of tyrosine protein kinase inhibitors.

1990 ◽  
Vol 265 (36) ◽  
pp. 22255-22261
Author(s):  
J F Geissler ◽  
P Traxler ◽  
U Regenass ◽  
B J Murray ◽  
J L Roesel ◽  
...  
Keyword(s):  
Biological Activity ◽  
Protein Kinase ◽  
Kinase Inhibitors ◽  
Protein Kinase Inhibitors ◽  
Tyrosine Protein Kinase
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