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Protein kinase C recognizes the protein kinase A-binding motif of nonstructural protein 3 of hepatitis C virus

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Protein kinase C recognizes the protein kinase A-binding motif of nonstructural protein 3 of hepatitis C virus. / Borowski, P; Schulze zur Wiesch, J; Resch, K; Feucht, H; Laufs, R; Schmitz, H.

In: J BIOL CHEM, Vol. 274, No. 43, 22.10.1999, p. 30722-8.

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

Harvard

Borowski, P, Schulze zur Wiesch, J, Resch, K, Feucht, H, Laufs, R & Schmitz, H 1999, 'Protein kinase C recognizes the protein kinase A-binding motif of nonstructural protein 3 of hepatitis C virus', J BIOL CHEM, vol. 274, no. 43, pp. 30722-8. https://doi.org/10.1074/jbc.274.43.30722

APA

Borowski, P., Schulze zur Wiesch, J., Resch, K., Feucht, H., Laufs, R., & Schmitz, H. (1999). Protein kinase C recognizes the protein kinase A-binding motif of nonstructural protein 3 of hepatitis C virus. J BIOL CHEM, 274(43), 30722-8. https://doi.org/10.1074/jbc.274.43.30722

Vancouver

Borowski P, Schulze zur Wiesch J, Resch K, Feucht H, Laufs R, Schmitz H. Protein kinase C recognizes the protein kinase A-binding motif of nonstructural protein 3 of hepatitis C virus. J BIOL CHEM. 1999 Oct 22;274(43):30722-8. https://doi.org/10.1074/jbc.274.43.30722

Bibtex

@article{160f1dee8d40404dbc76b494f4575f9b,
title = "Protein kinase C recognizes the protein kinase A-binding motif of nonstructural protein 3 of hepatitis C virus",
abstract = "The nonstructural protein 3 (NS3) of hepatitis C virus (HCV) inhibits the nuclear transport and the enzymatic activity of the catalytic subunit of protein kinase A. This inhibition is mediated by an arginine-rich domain localized between amino acids 1487-1500 of the HCV polyprotein. The data presented here indicate that the arginine-rich domain, when embedded in recombinant fragments of NS3, interacts with the catalytic site of protein kinase C (PKC) and inhibits the phosphorylation mediated by this enzyme in vitro and in vivo. Furthermore, a direct binding of PKC to the NS3 fragments leads to an inhibition of the free shuttling of the kinase between the cytoplasm and the particulate fraction. In contrast, a peptide corresponding to the arginine-rich domain (HCV (1487-1500)), despite also being a PKC inhibitor, did not influence the PKC shuttling process and was transported to the particulate fraction by the translocating kinase upon activation with tetradecanoylphorbol-13-acetate. Using the tetradecanoylphorbol-13-acetate -stimulated respiratory burst of NS3-introduced neutrophils as a model system, we could demonstrate that NS3 is able to block PKC-mediated functions within intact cells. Our data support the possibility that NS3 disrupts the PKC-mediated signal transduction.",
keywords = "Amino Acid Sequence, Animals, Arginine, Binding Sites, Brain/enzymology, Cloning, Molecular, Cyclic AMP-Dependent Protein Kinases/metabolism, Enzyme Activation, Hepacivirus/metabolism, Humans, Kinetics, Neutrophils/enzymology, Peptide Fragments/chemistry, Protein Kinase C/metabolism, Rats, Recombinant Proteins/chemistry, Tetradecanoylphorbol Acetate/pharmacology, Viral Nonstructural Proteins/chemistry",
author = "P Borowski and {Schulze zur Wiesch}, J and K Resch and H Feucht and R Laufs and H Schmitz",
year = "1999",
month = oct,
day = "22",
doi = "10.1074/jbc.274.43.30722",
language = "English",
volume = "274",
pages = "30722--8",
journal = "J BIOL CHEM",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "43",

}

RIS

TY - JOUR

T1 - Protein kinase C recognizes the protein kinase A-binding motif of nonstructural protein 3 of hepatitis C virus

AU - Borowski, P

AU - Schulze zur Wiesch, J

AU - Resch, K

AU - Feucht, H

AU - Laufs, R

AU - Schmitz, H

PY - 1999/10/22

Y1 - 1999/10/22

N2 - The nonstructural protein 3 (NS3) of hepatitis C virus (HCV) inhibits the nuclear transport and the enzymatic activity of the catalytic subunit of protein kinase A. This inhibition is mediated by an arginine-rich domain localized between amino acids 1487-1500 of the HCV polyprotein. The data presented here indicate that the arginine-rich domain, when embedded in recombinant fragments of NS3, interacts with the catalytic site of protein kinase C (PKC) and inhibits the phosphorylation mediated by this enzyme in vitro and in vivo. Furthermore, a direct binding of PKC to the NS3 fragments leads to an inhibition of the free shuttling of the kinase between the cytoplasm and the particulate fraction. In contrast, a peptide corresponding to the arginine-rich domain (HCV (1487-1500)), despite also being a PKC inhibitor, did not influence the PKC shuttling process and was transported to the particulate fraction by the translocating kinase upon activation with tetradecanoylphorbol-13-acetate. Using the tetradecanoylphorbol-13-acetate -stimulated respiratory burst of NS3-introduced neutrophils as a model system, we could demonstrate that NS3 is able to block PKC-mediated functions within intact cells. Our data support the possibility that NS3 disrupts the PKC-mediated signal transduction.

AB - The nonstructural protein 3 (NS3) of hepatitis C virus (HCV) inhibits the nuclear transport and the enzymatic activity of the catalytic subunit of protein kinase A. This inhibition is mediated by an arginine-rich domain localized between amino acids 1487-1500 of the HCV polyprotein. The data presented here indicate that the arginine-rich domain, when embedded in recombinant fragments of NS3, interacts with the catalytic site of protein kinase C (PKC) and inhibits the phosphorylation mediated by this enzyme in vitro and in vivo. Furthermore, a direct binding of PKC to the NS3 fragments leads to an inhibition of the free shuttling of the kinase between the cytoplasm and the particulate fraction. In contrast, a peptide corresponding to the arginine-rich domain (HCV (1487-1500)), despite also being a PKC inhibitor, did not influence the PKC shuttling process and was transported to the particulate fraction by the translocating kinase upon activation with tetradecanoylphorbol-13-acetate. Using the tetradecanoylphorbol-13-acetate -stimulated respiratory burst of NS3-introduced neutrophils as a model system, we could demonstrate that NS3 is able to block PKC-mediated functions within intact cells. Our data support the possibility that NS3 disrupts the PKC-mediated signal transduction.

KW - Amino Acid Sequence

KW - Animals

KW - Arginine

KW - Binding Sites

KW - Brain/enzymology

KW - Cloning, Molecular

KW - Cyclic AMP-Dependent Protein Kinases/metabolism

KW - Enzyme Activation

KW - Hepacivirus/metabolism

KW - Humans

KW - Kinetics

KW - Neutrophils/enzymology

KW - Peptide Fragments/chemistry

KW - Protein Kinase C/metabolism

KW - Rats

KW - Recombinant Proteins/chemistry

KW - Tetradecanoylphorbol Acetate/pharmacology

KW - Viral Nonstructural Proteins/chemistry

U2 - 10.1074/jbc.274.43.30722

DO - 10.1074/jbc.274.43.30722

M3 - SCORING: Journal article

C2 - 10521461

VL - 274

SP - 30722

EP - 30728

JO - J BIOL CHEM

JF - J BIOL CHEM

SN - 0021-9258

IS - 43

ER -