scholarly journals Regulation of Nramp1 mRNA stability by oxidants and protein kinase C in RAW264.7 macrophages expressing Nramp1Gly169

2000 ◽  
Vol 351 (3) ◽  
pp. 687-696 ◽  
Author(s):  
William P. LAFUSE ◽  
Gail R. ALVAREZ ◽  
Bruce S. ZWILLING
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Mrna Stability ◽  
Pleiotropic Effects ◽  
Natural Resistance ◽  
Raw264.7 Macrophages ◽  
Kinase C ◽  
Wide Range ◽  
Macrophage Protein ◽  
The Stability

The murine Nramp1 (natural-resistance-associated macrophage protein) locus confers innate resistance against intracellular macrophage pathogens. The gene encodes a transporter molecule, which is rapidly recruited to the phagosome. Nramp1 functions as an iron transporter by transporting iron into the phagosome. Within the phagosome iron mediates anti-microbial killing by hydroxyl radical formation through the iron-catalysed Fenton/Haber–Weiss reaction. In addition to its effects on the growth of intracellular pathogens, Nramp1 exerts a wide range of pleiotropic effects in activated macrophages. One of these pleiotropic effects is the increased stability of a variety of mRNA species, including Nramp1 mRNA. In the present study, the stability of Nramp1 mRNA in Mycobacterium avium infected RAW264.7 macrophages expressing either the Nramp1Gly169 resistant allele or the Nramp1Asp169 susceptible allele was examined. Nramp1 mRNA stability was greater in Nramp1Gly169 macrophages than in Nramp1Asp169 macrophages. The increase in Nramp1 mRNA stability in resistant macrophages was inhibited by antioxidants and protein kinase C (PKC) inhibitors, suggesting that Nramp1 mRNA stability is regulated by an oxidant-generated signalling pathway that requires PKC activity. This was corroborated by treating Nramp1Asp169 macrophages with menadione, which generates reactive oxygen species within cells. Menadione increased Nramp1 mRNA stability to the level observed in resistant macrophages; this increase was also inhibited by a PKC inhibitor. Further, PKC activity was found to be greater in M. avium-infected Nramp1Gly169 macrophages than in infected Nramp1Asp169 macrophages and inhibited by treatment with an antioxidant.

scholarly journals Regulation of mammalian ribonucleotide reductase R1 mRNA stability is mediated by a ribonucleotide reductase R1 mRNA 3′-untranslated region cis-trans interaction through a protein kinase C-controlled pathway

1994 ◽  
Vol 302 (1) ◽  
pp. 125-132 ◽  
Author(s):  
F Y Chen ◽  
F M Amara ◽  
J A Wright
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Okadaic Acid ◽  
Ribonucleotide Reductase ◽  
Mrna Stability ◽  
Untranslated Region ◽  
Rna Binding ◽  
Kinase C ◽  
The Stability ◽  
Dose Dependent

Ribonucleotide reductase catalyses the reaction that eventually provides the four deoxyribonucleotides required for the synthesis and repair of DNA. U.v.-cross-linking and band-shift experiments have identified in COS 7 monkey cells an approx. 57 kDa ribonucleotide reductase R1 mRNA-binding protein called R1BP, which binds specifically to a 49-nt region of the R1 mRNA 3′-untranslated region (3′UTR). The R1BP-RNA binding activity was down-regulated by the tumour promoters phorbol 12-myristate 13-acetate (PMA; ‘TPA’) and okadaic acid, and up-regulated by the protein kinase C inhibitor staurosporine, in a dose-dependent fashion. Furthermore, staurosporine treatment decreased the stability of R1 and CAT (chloramphenicol acetyltransferase)/R1 hybrid mRNAs, whereas PMA and okadaic acid increased the stability of these messages, in a dose-dependent manner. In contrast, treatment of cells with forskolin, a protein kinase A inhibitor, did not alter either R1BP-RNA binding or R1 mRNA-stability characteristics. Transfectants containing R1 or CAT/R1 cDNA constructs with a deletion of the 49-nt 3′UTR sequence failed to respond in message-stability studies to the effects of PMA, staurosporine or okadaic acid. These observations indicate that a protein kinase C signal pathway regulates ribonucleotide reductase R1 gene expression post-transcriptionally, through a mechanism involving a specific cis-trans interaction at a 49-nt region within the R1 mRNA 3′UTR.

scholarly journals Protein kinase C-δ regulates the stability of hypoxia-inducible factor-1α under hypoxia

2007 ◽  
Vol 98 (9) ◽  
pp. 1476-1481 ◽  
Author(s):  
Ji-Won Lee ◽  
Jeong Ae Park ◽  
Se-Hee Kim ◽  
Ji Hae Seo ◽  
Kyung-Joon Lim ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1Α ◽  
Kinase C ◽  
The Stability

PMA and staurosporine affect expression of the PCK gene in LLC-PK1-F+cells

1998 ◽  
Vol 275 (3) ◽  
pp. F361-F369 ◽  
Author(s):  
Wenlin Liu ◽  
Elisabeth Feifel ◽  
Thomas Holcomb ◽  
Xiangdong Liu ◽  
Nikolaus Spitaler ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Half Life ◽  
Rapid Decrease ◽  
Prolonged Treatment ◽  
Camp Response Element ◽  
Kinase C ◽  
F Cells ◽  
Chloramphenicol Acetyltransferase Gene ◽  
The Stability

The addition of phorbol 12-myristate 13-acetate (PMA) to renal LLC-PK1-F+cells caused a rapid decrease in the level of phospho enolpyruvate carboxykinase (PCK) mRNA and reversed the stimulatory effects of exposure to acidic medium (pH 6.9, 10 mM [Formula: see text]) or cAMP. In contrast, prolonged treatment with PMA increased the levels of PCK mRNA. The two effects correlated with the membrane translocation and downregulation of the α-isozyme of protein kinase C and were blocked by pretreatment with specific inhibitors of protein kinase C. The rapid decrease in PCK mRNA caused by PMA occurred with a half-life ( t ½ = 1 h) that is significantly faster than that measured during recovery from acid medium or following inhibition of transcription ( t ½ = 4 h). The effect of PMA was reversed by staurosporine, which apparently acts by inhibiting a signaling pathway other than protein kinase C. Staurosporine had no effect on the half-life of the PCK mRNA, but it stimulated the activity of a chloramphenicol acetyltransferase gene that was driven by the initial 490 base pairs of the PCK promoter and transiently transfected into LLC-PK1-F+cells. This effect was additive to that of cAMP, and neither stimulation was reversed by PMA. The stimulatory effect of staurosporine was mapped to the cAMP response element (CRE-1) and P3(II) element of the PCK promoter. The data indicate that, in LLC-PK1-F+cells, activation of protein kinase C decreases the stability of the PCK mRNA, whereas transcription of the PCK gene may be suppressed by a kinase that is inhibited by staurosporine.

scholarly journals Post-transcriptional regulation of H-ferritin gene expression in human monocytic THP-1 cells by protein kinase C

1996 ◽  
Vol 319 (1) ◽  
pp. 185-189 ◽  
Author(s):  
Jong-Hwei S. PANG ◽  
Chia-Jung WU ◽  
Lee-Young CHAU
Keyword(s):  
Gene Expression ◽  
Protein Synthesis ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Human Fibroblasts ◽  
Leukaemic Cell ◽  
Protein Synthesis Inhibitor ◽  
Kinase C ◽  
Ferritin Gene ◽  
The Stability

The mRNA coding for H-ferritin was highly induced in human monocytic THP-1 cells following treatment with phorbol 12-myristate 13-acetate (PMA). The induction was detected at 3 h, reached maximal levels at 12 h, and was sustained for up to 48 h subsequent to PMA exposure. PMA-induced up-regulation of H-ferritin gene expression was also observed in other leukaemic cell lines, HL60 and U937, but not in non-leukaemic cell types, including human fibroblasts, endothelial cells and smooth muscle cells. The effect of PMA could be completely blocked by the protein kinase C inhibitor, H-7. Furthermore, treatment of THP-1 cells with bacterial phospholipase C also produced a marked increase in expression of H-ferritin mRNA, suggesting the activation of protein kinase C was responsible for the accumulation of mRNA. Nuclear run-off experiments demonstrated that PMA did not increase the transcriptional rate of the H-ferritin gene. In contrast, the half-life of the H-ferritin mRNA measured in the presence of actinomycin D was greatly prolonged in PMA-treated cells. The induction of H-ferritin mRNA by PMA required no protein synthesis. Conversely, treatment of THP-1 cells with protein synthesis inhibitor, cycloheximide, resulted in a 4–5-fold increase in H-ferritin mRNA. The increase in the stability of the H-ferritin mRNA was also observed in cells treated with cycloheximide. Taken together, these results suggest that the stability of H-ferritin mRNA in THP-1 is subjected to regulation via a protein kinase C-mediated phosphorylation on existing putative protein factor(s).

scholarly journals Regulated expression of endothelin converting enzymes in glomerular endothelial cells.

1997 ◽  
Vol 8 (4) ◽  
pp. 580-585 ◽  
Author(s):  
K Uchida ◽  
S Uchida ◽  
K Nitta ◽  
W Yumura ◽  
H Nihei
Keyword(s):  
Endothelial Cells ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Transcriptional Activation ◽  
Mrna Stability ◽  
Ribonuclease Protection Assay ◽  
Signaling Systems ◽  
Control Value ◽  
Kinase C ◽  
Glomerular Endothelial Cells

Endothelin converting enzyme (ECE) constitutes a potential regulatory site for the production of active mature endothelins. Two cDNAs (ECE-1 and -2) encoding ECE have recently been cloned, but the regulation of the expression of these ECE has not been clarified. In the study presented here, an attempt was made to determine whether or not glomerular endothelial cells (GEN) express ECE-1 and -2, and to learn how the expression of ECE-1 and -2 is regulated by kinase-mediated signaling systems. Ribonuclease protection assay revealed the expression of ECE-1 and -2 in cultured GEN, and the expression was increased approximately 2.5- and approximately 1.8-fold, respectively, by treatment with 10(-7) M 12-O-tetradecanocyl-phorbol-13-acetate (TPA) for 4 hours. These increases in ECE-1 and -2 expression with TPA were inhibited by cotreatment with calphostin C (10(-7) M). In contrast, 24-h treatment with 10(-7) M TPA significantly decreased the expression of ECE-1 and -2, indicating that the expression was tightly regulated by protein kinase C (PKC)-dependent mechanism(s). Actinomycin D (1 microgram/mL) abolished the TPA-induced increase of ECE-1 and -2 mRNA, whereas TPA treatment did not affect the mRNA stability of ECE-1 and -2, thus suggesting that TPA-induced increases of ECE-1 and -2 mRNA resulted from the transcriptional activation of ECE-1 and -2, gene, rather than from the increase of mRNA stability. In addition to the regulation by PKC, the effects of protein kinase A and G on ECE-1 and -2 expression were also examined. Treatment with chlorophenyl-thio cyclic AMP (200 microM) for 24 h decreased ECE-1 and -2 expression to approximately 50% and approximately 40% of the control value, respectively. 8-bromo-3', 5'-cyclic GMP also decreased ECE-1 and -2 expression to approximately 80% and approximately 25% of the control value, respectively. These results demonstrate that the expression of ECE-1 and -2 is regulated by kinase-mediated signaling systems, with the most prominent regulatory effect shown by protein kinase C.

scholarly journals Protein kinase C mechanisms that contribute to cardiac remodelling

2016 ◽  
Vol 130 (17) ◽  
pp. 1499-1510 ◽  
Author(s):  
Alexandra C. Newton ◽  
Corina E. Antal ◽  
Susan F. Steinberg
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Protein Phosphorylation ◽  
Cardiac Contractility ◽  
Cellular Responses ◽  
Growth Responses ◽  
Kinase C ◽  
Wide Range ◽  
Clinical Disorders

Protein phosphorylation is a highly-regulated and reversible process that is precisely controlled by the actions of protein kinases and protein phosphatases. Factors that tip the balance of protein phosphorylation lead to changes in a wide range of cellular responses, including cell proliferation, differentiation and survival. The protein kinase C (PKC) family of serine/threonine kinases sits at nodal points in many signal transduction pathways; PKC enzymes have been the focus of considerable attention since they contribute to both normal physiological responses as well as maladaptive pathological responses that drive a wide range of clinical disorders. This review provides a background on the mechanisms that regulate individual PKC isoenzymes followed by a discussion of recent insights into their role in the pathogenesis of diseases such as cancer. We then provide an overview on the role of individual PKC isoenzymes in the regulation of cardiac contractility and pathophysiological growth responses, with a focus on the PKC-dependent mechanisms that regulate pump function and/or contribute to the pathogenesis of heart failure.

Analysis of Protein Kinase C Isoforms Involved in the Activation of Laminin Receptor in Raw264.7 Macrophages

IUBMB Life ◽  
1999 ◽  
Vol 48 (4) ◽  
pp. 439-443 ◽  
Author(s):  
Chun-Do Oh ◽  
Shin-Sung Kang ◽  
Mahn Joon Ha ◽  
Jang-Soo Chun
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Laminin Receptor ◽  
Raw264.7 Macrophages ◽  
Kinase C ◽  
Protein Kinase C Isoforms

scholarly journals PICK1: a perinuclear binding protein and substrate for protein kinase C isolated by the yeast two-hybrid system.

1995 ◽  
Vol 128 (3) ◽  
pp. 263-271 ◽  
Author(s):  
J Staudinger ◽  
J Zhou ◽  
R Burgess ◽  
S J Elledge ◽  
E N Olson
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Hybrid System ◽  
Catalytic Domain ◽  
Yeast Two Hybrid ◽  
Kinase C ◽  
Yeast Two Hybrid System ◽  
Wide Range ◽  
Two Hybrid

Protein kinase C (PKC) plays a central role in the control of proliferation and differentiation of a wide range of cell types by mediating the signal transduction response to hormones and growth factors. Upon activation by diacylglycerol, PKC translocates to different subcellular sites where it phosphorylates numerous proteins, most of which are unidentified. We used the yeast two-hybrid system to identify proteins that interact with activated PKC alpha. Using the catalytic region of PKC fused to the DNA binding domain of yeast GAL4 as "bait" to screen a mouse T cell cDNA library in which cDNA was fused to the GAL4 activation domain, we cloned several novel proteins that interact with C-kinase (PICKs). One of these proteins, designated PICK1, interacts specifically with the catalytic domain of PKC and is an efficient substrate for phosphorylation by PKC in vitro and in vivo. PICK1 is localized to the perinuclear region and is phosphorylated in response to PKC activation. PICK1 and other PICKs may play important roles in mediating the actions of PKC.

Sign in / Sign up

Export Citation Format

Share Document