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Characterisation of non-structural protein 3 of hepatitis C virus as modulator of protein phosphorylation mediated by PKA and PKC

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Characterisation of non-structural protein 3 of hepatitis C virus as modulator of protein phosphorylation mediated by PKA and PKC : evidences for action on the level of substrate and enzyme. / Borowski, P; Heiland, M; Feucht, H; Laufs, R.

In: ARCH VIROL, Vol. 144, No. 4, 01.01.1999, p. 687-701.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Borowski, P, Heiland, M, Feucht, H & Laufs, R 1999, 'Characterisation of non-structural protein 3 of hepatitis C virus as modulator of protein phosphorylation mediated by PKA and PKC: evidences for action on the level of substrate and enzyme', ARCH VIROL, vol. 144, no. 4, pp. 687-701.

APA

Borowski, P., Heiland, M., Feucht, H., & Laufs, R. (1999). Characterisation of non-structural protein 3 of hepatitis C virus as modulator of protein phosphorylation mediated by PKA and PKC: evidences for action on the level of substrate and enzyme. ARCH VIROL, 144(4), 687-701.

Vancouver

Borowski P, Heiland M, Feucht H, Laufs R. Characterisation of non-structural protein 3 of hepatitis C virus as modulator of protein phosphorylation mediated by PKA and PKC: evidences for action on the level of substrate and enzyme. ARCH VIROL. 1999 Jan 1;144(4):687-701.

Bibtex

@article{3bb4730d9d4042d2a07d16596074f1f1,
title = "Characterisation of non-structural protein 3 of hepatitis C virus as modulator of protein phosphorylation mediated by PKA and PKC: evidences for action on the level of substrate and enzyme",
abstract = "Generally, the maximum activities of the protein kinases A (PKA) and C (PKC) show an optimum value for their substrate concentrations rather than a saturation curve; at high substrate concentrations, the kinase activity is completely abolished. The C- and N-truncated form of the non-structural protein 3 (NS3) of hepatitis C virus (HCV) (HCV-polyprotein-(1,189-1,525)) abolishes the inhibiting effect of the substrate, yielding saturable Michaelis-Menten kinetics of PKA and its catalytical domain (C subunit). In contrast, HCV-polyprotein-(1,189-1,525) activates PKC with increasing Vmax, while it abolishes the substrate inhibition of its catalytical domain (M-kinase) through a mechanism analogous to that of PKA and C subunit. PKC isoforms alpha, beta and gamma investigated are similarly activated by HCV-polyprotein-(1,189-1,525). Our data suggest that NS3 attenuates the substrate inhibition through a generalized mechanism operating mainly on the substrate level that directly results from a specific protein-protein interaction. In the case of the PKC, an additional kinase activating mechanism operates on the enzyme level. Both actions of NS3, the attenuation of the substrate inhibition and the activation of PKC, could not be explained by classical means that predict autophosphorylation to enhance the rate of substrate phosphorylation. The results are discussed in view of similar activities displayed by matchmakers and some molecular chaperones.",
keywords = "Alkylation, Animals, Brain, Cloning, Molecular, Cyclic AMP-Dependent Protein Kinases, Hepacivirus, Histones, Isoenzymes, Kinetics, Oxidation-Reduction, Phosphorylation, Protein Kinase C, Protein Kinase C beta, Protein Kinase C-alpha, Rats, Recombinant Fusion Proteins, Recombinant Proteins, Sequence Deletion, Viral Nonstructural Proteins",
author = "P Borowski and M Heiland and H Feucht and R Laufs",
year = "1999",
month = jan,
day = "1",
language = "English",
volume = "144",
pages = "687--701",
journal = "ARCH VIROL",
issn = "0304-8608",
publisher = "Springer Wien",
number = "4",

}

RIS

TY - JOUR

T1 - Characterisation of non-structural protein 3 of hepatitis C virus as modulator of protein phosphorylation mediated by PKA and PKC

T2 - evidences for action on the level of substrate and enzyme

AU - Borowski, P

AU - Heiland, M

AU - Feucht, H

AU - Laufs, R

PY - 1999/1/1

Y1 - 1999/1/1

N2 - Generally, the maximum activities of the protein kinases A (PKA) and C (PKC) show an optimum value for their substrate concentrations rather than a saturation curve; at high substrate concentrations, the kinase activity is completely abolished. The C- and N-truncated form of the non-structural protein 3 (NS3) of hepatitis C virus (HCV) (HCV-polyprotein-(1,189-1,525)) abolishes the inhibiting effect of the substrate, yielding saturable Michaelis-Menten kinetics of PKA and its catalytical domain (C subunit). In contrast, HCV-polyprotein-(1,189-1,525) activates PKC with increasing Vmax, while it abolishes the substrate inhibition of its catalytical domain (M-kinase) through a mechanism analogous to that of PKA and C subunit. PKC isoforms alpha, beta and gamma investigated are similarly activated by HCV-polyprotein-(1,189-1,525). Our data suggest that NS3 attenuates the substrate inhibition through a generalized mechanism operating mainly on the substrate level that directly results from a specific protein-protein interaction. In the case of the PKC, an additional kinase activating mechanism operates on the enzyme level. Both actions of NS3, the attenuation of the substrate inhibition and the activation of PKC, could not be explained by classical means that predict autophosphorylation to enhance the rate of substrate phosphorylation. The results are discussed in view of similar activities displayed by matchmakers and some molecular chaperones.

AB - Generally, the maximum activities of the protein kinases A (PKA) and C (PKC) show an optimum value for their substrate concentrations rather than a saturation curve; at high substrate concentrations, the kinase activity is completely abolished. The C- and N-truncated form of the non-structural protein 3 (NS3) of hepatitis C virus (HCV) (HCV-polyprotein-(1,189-1,525)) abolishes the inhibiting effect of the substrate, yielding saturable Michaelis-Menten kinetics of PKA and its catalytical domain (C subunit). In contrast, HCV-polyprotein-(1,189-1,525) activates PKC with increasing Vmax, while it abolishes the substrate inhibition of its catalytical domain (M-kinase) through a mechanism analogous to that of PKA and C subunit. PKC isoforms alpha, beta and gamma investigated are similarly activated by HCV-polyprotein-(1,189-1,525). Our data suggest that NS3 attenuates the substrate inhibition through a generalized mechanism operating mainly on the substrate level that directly results from a specific protein-protein interaction. In the case of the PKC, an additional kinase activating mechanism operates on the enzyme level. Both actions of NS3, the attenuation of the substrate inhibition and the activation of PKC, could not be explained by classical means that predict autophosphorylation to enhance the rate of substrate phosphorylation. The results are discussed in view of similar activities displayed by matchmakers and some molecular chaperones.

KW - Alkylation

KW - Animals

KW - Brain

KW - Cloning, Molecular

KW - Cyclic AMP-Dependent Protein Kinases

KW - Hepacivirus

KW - Histones

KW - Isoenzymes

KW - Kinetics

KW - Oxidation-Reduction

KW - Phosphorylation

KW - Protein Kinase C

KW - Protein Kinase C beta

KW - Protein Kinase C-alpha

KW - Rats

KW - Recombinant Fusion Proteins

KW - Recombinant Proteins

KW - Sequence Deletion

KW - Viral Nonstructural Proteins

M3 - SCORING: Journal article

C2 - 10365161

VL - 144

SP - 687

EP - 701

JO - ARCH VIROL

JF - ARCH VIROL

SN - 0304-8608

IS - 4

ER -