scholarly journals Possible Involvement of Atypical Protein Kinase C(PKC) in Glucose-Sensitive Expression of the Human Insulin Gene: DNA-Binding Activity and Transcriptional Activity of Pancreatic and Duodenal Homeobox Gene-1(PDX-1) Are Enhanced via Calphostin C-Sensitive but Phorbol 12-Myristate 13-Acetate(PMA) and Goe 6976-Insensitive Pathway.

1999 ◽  
Vol 46 (1) ◽  
pp. 43-58 ◽  
Author(s):  
NOBORU FURUKAWA ◽  
TETSUYA SHIROTANI ◽  
EIICHI ARAKI ◽  
KENGO KANEKO ◽  
MIKIO TODAKA ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Dna Binding ◽  
Transcriptional Activity ◽  
Homeobox Gene ◽  
Binding Activity ◽  
Calphostin C ◽  
Dna Binding Activity ◽  
Kinase C ◽  
Human Insulin Gene

Activation of protein kinase C decreases phosphorylation of c-Jun at sites that negatively regulate its DNA-binding activity

Cell ◽  
1991 ◽  
Vol 64 (3) ◽  
pp. 573-584 ◽  
Author(s):  
William J. Boyle ◽  
Tod Smeal ◽  
Libert H.K. Defize ◽  
Peter Angel ◽  
James R. Woodgett ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Dna Binding ◽  
Binding Activity ◽  
Dna Binding Activity ◽  
Kinase C

scholarly journals Cross-coupling of signal transduction pathways: the dioxin receptor mediates induction of cytochrome P-450IA1 expression via a protein kinase C-dependent mechanism.

1993 ◽  
Vol 13 (1) ◽  
pp. 677-689 ◽  
Author(s):  
A Berghard ◽  
K Gradin ◽  
I Pongratz ◽  
M Whitelaw ◽  
L Poellinger
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Dna Binding ◽  
Binding Activity ◽  
Dna Binding Activity ◽  
Kinase C ◽  
The Individual ◽  
Dioxin Receptor

Signal transduction by dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin) is mediated by the intracellular dioxin receptor which, in its dioxin-activated state, regulates transcription of target genes encoding drug-metabolizing enzymes, such as cytochrome P-450IA1 and glutathione S-transferase Ya. Exposure of the dioxin receptor to dioxin leads to an apparent translocation of the receptor to the nucleus in vivo and to a rapid conversion of the receptor from a latent, non-DNA-binding form to a species that binds to dioxin-responsive positive control elements in vitro. This DNA-binding form of receptor appears to be a heterodimeric complex with the helix-loop-helix factor Arnt. In this study, we show that activation of the cytochrome P-450IA1 gene and minimal dioxin-responsive reporter constructs by the dioxin receptor was inhibited following prolonged treatment of human keratinocytes with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate. Inhibition of the receptor-mediated activation response was also achieved by treatment of the cells with a number of protein kinase inhibitors, one of which, calphostin C, shows selectivity for protein kinase C. Taken together, these data suggest that protein kinase C-dependent phosphorylation may play an essential role in the dioxin signaling pathway. This hypothesis is supported by the observation that pretreatment of the cells with 12-O-tetradecanoylphorbol-13-acetate inhibited the DNA-binding activity of the dioxin receptor in vivo. In vivo, the dioxin receptor was found to be a phosphoprotein. In vitro, dephosphorylation of the ligand-activated, heteromeric dioxin receptor form or dephosphorylation of the individual ligand-binding and Arnt receptor subunits inhibited the xenobiotic response element-binding activity. Moreover, dephosphorylation experiments with the individual receptor subunits prior to assembly of the xenobiotic response element-binding receptor form indicated that phosphorylation seemed to be important for the DNA-binding activity per se of the receptor, whereas Arnt appeared to require phosphorylation to interact with the receptor. Finally, a protein kinase C inhibitor-sensitive cytosolic catalytic activity that could restore the DNA-binding activity of the dephosphorylated dioxin receptor form was identified.

scholarly journals Aggregation of the FcRI in Mast Cells Induces the Synthesis of Fos-interacting Protein and Increases Its DNA Binding Activity: The Dependence on Protein Kinase C-

1996 ◽  
Vol 271 (3) ◽  
pp. 1514-1519 ◽  
Author(s):  
Iris Lewin ◽  
Jasmine Jacob-Hirsch ◽  
Zhao Cheng Zang ◽  
Valentina Kupershtein ◽  
Zoltan Szallasi ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Mast Cells ◽  
Protein Kinase ◽  
Dna Binding ◽  
Binding Activity ◽  
Interacting Protein ◽  
Dna Binding Activity ◽  
Kinase C

Cross-coupling of signal transduction pathways: the dioxin receptor mediates induction of cytochrome P-450IA1 expression via a protein kinase C-dependent mechanism

1993 ◽  
Vol 13 (1) ◽  
pp. 677-689
Author(s):  
A Berghard ◽  
K Gradin ◽  
I Pongratz ◽  
M Whitelaw ◽  
L Poellinger
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Dna Binding ◽  
Binding Activity ◽  
Dna Binding Activity ◽  
Kinase C ◽  
The Individual ◽  
Dioxin Receptor

Signal transduction by dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin) is mediated by the intracellular dioxin receptor which, in its dioxin-activated state, regulates transcription of target genes encoding drug-metabolizing enzymes, such as cytochrome P-450IA1 and glutathione S-transferase Ya. Exposure of the dioxin receptor to dioxin leads to an apparent translocation of the receptor to the nucleus in vivo and to a rapid conversion of the receptor from a latent, non-DNA-binding form to a species that binds to dioxin-responsive positive control elements in vitro. This DNA-binding form of receptor appears to be a heterodimeric complex with the helix-loop-helix factor Arnt. In this study, we show that activation of the cytochrome P-450IA1 gene and minimal dioxin-responsive reporter constructs by the dioxin receptor was inhibited following prolonged treatment of human keratinocytes with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate. Inhibition of the receptor-mediated activation response was also achieved by treatment of the cells with a number of protein kinase inhibitors, one of which, calphostin C, shows selectivity for protein kinase C. Taken together, these data suggest that protein kinase C-dependent phosphorylation may play an essential role in the dioxin signaling pathway. This hypothesis is supported by the observation that pretreatment of the cells with 12-O-tetradecanoylphorbol-13-acetate inhibited the DNA-binding activity of the dioxin receptor in vivo. In vivo, the dioxin receptor was found to be a phosphoprotein. In vitro, dephosphorylation of the ligand-activated, heteromeric dioxin receptor form or dephosphorylation of the individual ligand-binding and Arnt receptor subunits inhibited the xenobiotic response element-binding activity. Moreover, dephosphorylation experiments with the individual receptor subunits prior to assembly of the xenobiotic response element-binding receptor form indicated that phosphorylation seemed to be important for the DNA-binding activity per se of the receptor, whereas Arnt appeared to require phosphorylation to interact with the receptor. Finally, a protein kinase C inhibitor-sensitive cytosolic catalytic activity that could restore the DNA-binding activity of the dephosphorylated dioxin receptor form was identified.

scholarly journals Induction of the DNA-binding activity of c-jun/c-fos heterodimers by the hepatitis B virus transactivator pX.

1994 ◽  
Vol 14 (2) ◽  
pp. 989-998 ◽  
Author(s):  
G Natoli ◽  
M L Avantaggiati ◽  
P Chirillo ◽  
A Costanzo ◽  
M Artini ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Hepatitis B Virus ◽  
Protein Kinase ◽  
Dna Binding ◽  
Hepatitis B ◽  
Cell Lines ◽  
Binding Activity ◽  
Dna Binding Activity ◽  
Kinase C ◽  
B Virus

The hepatitis B virus (HBV) X protein (pX) is capable of activating transcription regulated by viral and cellular promoters containing binding sites for different transcription factors, including AP1. In this study we have analyzed the mechanisms of AP1 induction by pX. The hepatitis B virus transactivator was able to activate TRE (12-O-tetradecanoylphorbol-13-acetate response element)-directed transcription in different cell lines, including HepG2, HeLa, CV1, and PLC/PRF/5 cells. pX-induced AP1 activation in HepG2 cells was associated with an increase in the DNA-binding activity of c-Jun/c-Fos heterodimers, which was not dependent either on an increase in the overall amount of c-Fos and c-Jun proteins in the cells or on formation of dimers between pX and the two proteins, thus suggesting the involvement of posttranslational modifications of the transcription factor. The observation that the overexpression of c-Jun and c-Fos in the cells results in a strong augmentation of the effect of pX on TRE-directed transcription is additional evidence indicating the involvement of posttranscriptional modifications of c-Jun/c-Fos heterodimers. The increased AP1 binding observed in the presence of pX was unaffected by the protein kinase C inhibitors calphostin C and sphingosine and by the protein kinase A inhibitor HA1004, while it was almost completely blocked by staurosporine, a potent and nonspecific protein kinase inhibitor, suggesting that protein kinase C- and A-independent phosphorylation events might play a role in the phenomenon. The ability of pX also to increase TRE-directed transcription in cell lines in which AP1-binding activity is not increased (i.e., HeLa, CV1, and PLC/PRF/5 cells) suggests that pX can activate canonical TRE sites by different mechanisms as well.

High glucose-induced NF-κB activation occurs via tyrosine phosphorylation of IκBα in human glomerular endothelial cells: involvement of Syk tyrosine kinase

2008 ◽  
Vol 294 (5) ◽  
pp. F1065-F1075 ◽  
Author(s):  
Won Seok Yang ◽  
Jang Won Seo ◽  
Nam Jeong Han ◽  
Jung Choi ◽  
Ki-Up Lee ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Tyrosine Phosphorylation ◽  
High Glucose ◽  
Nuclear Translocation ◽  
Binding Activity ◽  
Serine Phosphorylation ◽  
Dna Binding Activity ◽  
Kinase C ◽  
Human Glomerular Endothelial Cells

Activation of nuclear factor-κB (NF-κB) occurs by dissociation from IκB after serine or tyrosine phosphorylation of IκBα, but the way of NF-κB activation by high glucose has not been defined. High glucose is known to activate NF-κB via protein kinase C and reactive oxygen species (ROS). In this study, we investigated how high glucose activates NF-κB for CC chemokine ligand 2 production in cultured human glomerular endothelial cells. High glucose increased nuclear translocation of p65 and also increased NF-κB DNA binding activity. High glucose-induced NF-κB activation occurred without degradation of IκBα. In agreement with this, there was no increase in serine phosphorylation of IκBα, while tyrosine phosphorylation of IκBα was increased by high glucose. High glucose increased the generation of ROS, whereas both α-lipoic acid and N-acetylcysteine scavenged the ROS and decreased high glucose-induced tyrosine phosphorylation of IκBα, nuclear translocation of p65, and NF-κB DNA binding activity. Protein kinase C pseudosubstrate inhibited high glucose-induced ROS production, tyrosine phosphorylation of IκBα, and nuclear translocation of p65. Both BAY 61-3606, a specific inhibitor of Syk protein-tyrosine kinase, and small interfering RNA directed against Syk inhibited high glucose-induced tyrosine phosphorylation of IκBα as well as p65 nuclear translocation. High glucose increased tyrosine phosphorylation of Syk, while it was inhibited by α-lipoic acid and protein kinase C pseudosubstrate. In summary, high glucose-induced NF-κB activation occurred not by serine phosphorylation of IκBα. Our data suggest that ROS-mediated tyrosine phosphorylation of IκBα is the mechanism for high glucose-induced NF-κB activation, and Syk may play a role in tyrosine phosphorylation of IκBα.

scholarly journals Hyperoxia, unlike phorbol ester, induces glutathione peroxidase through a protein kinase C-independent mechanism

1997 ◽  
Vol 326 (1) ◽  
pp. 117-123 ◽  
Author(s):  
Lan JORNOT ◽  
Alain F. JUNOD
Keyword(s):  
Protein Kinase C ◽  
Steady State ◽  
Protein Kinase ◽  
Glutathione Peroxidase ◽  
Binding Activity ◽  
Mrna Levels ◽  
Dna Binding Activity ◽  
Kinase C ◽  
Nuclear Extracts ◽  
Responsive Element

Human selenium-dependent glutathione peroxidase (GP) is implicated as a mechanism of resistance against oxygen free radicals. The 5′ flanking sequence upstream from the coding region of GP contained an oxygen-responsive element termed ORE1 that is responsive to hypoxia, as well as several copies of the activator protein-1 (AP-1)- and AP-1-like-binding sites. In this study, we sought to define the molecular events that lead to GP gene transcription in response to hyperoxia in human umbilical-vein endothelial cells, and asked whether such induction is mimicked and sustained by activation of protein kinase C (PKC) by phorbol esters. Treatment of cells with 100 nM phorbol 12,13-dibutyrate (PdBu) induced a delayed (24–48 h) but significant (2-fold) increase in steady-state GP mRNA levels. Steady-state GP mRNA levels also rose after exposure to 95% O2, again after considerable delay (48–72 h). For both PdBu and oxygen, induction was transcriptionally regulated, as demonstrated by nuclear run-on experiments. The simulations by PdBu and oxygen were additive. In contrast with PdBu, hyperoxia did not stimulate translocation of PKC from the cytosol to the particulate fraction, although the specific activity of both cytosolic and particulate-associated PKC was increased 2-fold in cells exposed to 95% O2 for 5 days. In addition, gel mobility-shift assays using double-stranded tumour-promoting-agent-responsive element (TRE) and nuclear extracts derived from phorbol- and oxygen-treated cells revealed that PdBu, but not hyperoxia, increased AP-1 DNA-binding activity. On the other hand, the up-regulation of GP expression by oxygen could not be accounted for by the ORE1 core sequence, since no specific protein–DNA binding activity could be detected using nuclear extracts from hyperoxic cells and ORE1. Taken together, these results suggest that there may be different molecular mechanisms controlling GP expression. After exposure to PdBu, GP undergoes transcriptional activation via a process that can be readily explained by a classic AP-1 interaction with the TRE sites in the GP promoter. During hyperoxia, GP also undergoes transcriptional activity, but via a process that appears to involve neither TRE nor ORE1.

scholarly journals Activation of the DNA-binding ability of latent p53 protein by protein kinase C is abolished by protein kinase CK2

2004 ◽  
Vol 378 (3) ◽  
pp. 939-947 ◽  
Author(s):  
Šárka POSPÍŠILOVÁ ◽  
Václav BRÁZDA ◽  
Kateřina KUCHAŘÍKOVÁ ◽  
M. Gloria LUCIANI ◽  
Ted R. HUPP ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Protein Kinase ◽  
Dna Binding ◽  
Protein Kinase Ck2 ◽  
P53 Protein ◽  
Cyclin A ◽  
Binding Activity ◽  
Dna Binding Activity ◽  
Kinase C ◽  
Kinase Ck2

p53 is one of the most important regulators of cell proliferation and differentiation and of programmed cell death, triggering growth arrest and/or apoptosis in response to different cellular stress signals. The sequence-specific DNA-binding function of p53 protein can be activated by several different stimuli that modulate the C-terminal domain of this protein. The predominant mechanism of activation of p53 sequence-specific DNA binding is phosphorylation at specific sites. For example, phosphorylation of p53 by PKC (protein kinase C) occurs in undamaged cells, resulting in masking of the epitope recognized by monoclonal antibody PAb421, and presumably promotes steady-state levels of p53 activity in cycling cells. In contrast, phosphorylation by cdk2 (cyclin-dependent kinase 2)/cyclin A and by the protein kinase CK2 are both enhanced in DNA-damaged cells. We determined whether one mechanism to account for this mutually exclusive phosphorylation may be that each phosphorylation event prevents modification by the other kinase. We used non-radioactive electrophoretic mobility shift assays to show that C-terminal phosphorylation of p53 protein by cdk2/cyclin A on Ser315 or by PKC on Ser378 can efficiently stimulate p53 binding to DNA in vitro, as well as binding of the monoclonal antibody Bp53-10, which recognizes residues 371–380 in the C-terminus of p53. Phosphorylation of p53 by CK2 on Ser392 induces its DNA-binding activity to a much lower extent than phosphorylation by cdk2/cyclin A or PKC. In addition, phosphorylation by CK2 strongly inhibits PKC-induced activation of p53 DNA binding, while the activation of p53 by cdk2/cyclin A is not affected by CK2. The presence of CK2-mediated phosphorylation promotes PKC binding to its docking site within the p53 oligomerization domain, but decreases phosphorylation by PKC, suggesting that competition between CK2 and PKC does not rely on the inhibition of PKC–p53 complex formation. These results indicate the crucial role of p53 C-terminal phosphorylation in the regulation of its DNA-binding activity, but also suggest that antagonistic relationships exist between different stress signalling pathways.

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