scholarly journals Protein Kinase C-Related Kinase 2 Phosphorylates the Protein Synthesis Initiation Factor eIF4E in Starfish Oocytes

2000 ◽  
Vol 228 (2) ◽  
pp. 166-180 ◽  
Author(s):  
Shyh-Jye Lee ◽  
Genevieve Stapleton ◽  
Julia H. Greene ◽  
Merrill B. Hille
Keyword(s):  
Protein Synthesis ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Initiation Factor ◽  
Kinase C ◽  
Protein Synthesis Initiation

scholarly journals Effect of vasopressin on the regulation of protein synthesis initiation in liver cells

1988 ◽  
Vol 254 (3) ◽  
pp. 773-779 ◽  
Author(s):  
J Menaya ◽  
R Parrilla ◽  
M S Ayuso
Keyword(s):  
Protein Synthesis ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Liver Cells ◽  
Initiation Factor ◽  
Protein Labelling ◽  
Kinase C ◽  
Isolated Liver Cells ◽  
Wide Range ◽  
Initiation Factor 2

Vasopressin was found to be an effective inhibitor of protein labelling in isolated liver cells. Its effect shows the following distinct characteristics: (1) in contrast with alpha-adrenergic agonists, its effect is observable under a wide range of cellular Ca2+-loading conditions; (2) it is not influenced by the nutritional state of the animal. The lack of vasopressin effect on valine production, and its ability to decrease protein labelling from near-saturation concentrations of [3H]valine, indicate that the observed variations in protein labelling reflect actual changes in the rate of protein synthesis. The action of vasopressin is primarily exerted on the initiation step of protein synthesis and this effect is accompanied by a decreased activity of eukaryotic initiation factor 2. Activators of protein kinase C showed similar but not additive effects on protein synthesis, as did vasopressin. It seems plausible to conclude that protein kinase C activation may play an important regulatory role in hepatic protein synthesis as a transducer of hormonal and perhaps other type of signals.

scholarly journals Ribosomal RACK1:Protein Kinase C βII Phosphorylates Eukaryotic Initiation Factor 4G1 at S1093 To Modulate Cap-Dependent and -Independent Translation Initiation

2018 ◽  
Vol 38 (19) ◽  
Author(s):  
Mikhail I. Dobrikov ◽  
Elena Y. Dobrikova ◽  
Matthias Gromeier
Keyword(s):  
Protein Synthesis ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Phorbol Ester ◽  
Kinase Inhibitor ◽  
Physiological Role ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Kinase C ◽  
Cox 2

ABSTRACT Eukaryotic ribosomes contain the high-affinity protein kinase C βII (PKCβII) scaffold, receptor for activated C kinase (RACK1), but its role in protein synthesis control remains unclear. We found that RACK1:PKCβII phosphorylates eukaryotic initiation factor 4G1 (eIF4G1) at S1093 and eIF3a at S1364. We showed that reversible eIF4G(S1093) phosphorylation is involved in a global protein synthesis surge upon PKC–Raf–extracellular signal-regulated kinase 1/2 (ERK1/2) activation and in induction of phorbol ester-responsive transcripts, such as cyclooxygenase 2 (Cox-2) and cyclin-dependent kinase inhibitor (p21Cip1), or in 5′ 7-methylguanosine (m7G) cap-independent enterovirus translation. Comparison of mRNA and protein levels revealed that eIF4G1 or RACK1 depletion blocked phorbol ester-induced Cox-2 or p21Cip1 expression mostly at the translational level, whereas PKCβ inhibition reduced them both at the translational and transcript levels. Our findings reveal a physiological role for ribosomal RACK1 in providing the molecular scaffold for PKCβII and its role in coordinating the translational response to PKC-Raf-ERK1/2 activation.

Dephosphorylation of activated protein kinase C contributes to downregulation by bryostatin

1996 ◽  
Vol 271 (1) ◽  
pp. C304-C311 ◽  
Author(s):  
H. W. Lee ◽  
L. Smith ◽  
G. R. Pettit ◽  
J. Bingham Smith
Keyword(s):  
Alkaline Phosphatase ◽  
Protein Synthesis ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Bryostatin 1 ◽  
Rapid Loss ◽  
Renal Epithelial Cells ◽  
Kinase C ◽  
Phosphatase Treatment ◽  
Pkc Alpha

We show that bryostatin 1 (Bryo) rapidly produces an inactive, incompetent 76-kDa form of protein kinase C-alpha (PKC-alpha) in the LLC-MK2 line of renal epithelial cells. Bryo, like phorbol 12-myristate 13-acetate (PMA), acutely activated PKC, as indicated by autophosphorylation and translocation of PKC-alpha, the predominant PMA-sensitive isoform expressed by the cells. Bryo concomitantly increased the 32P labeling of 80-kDa PKC-alpha by autophosphorylation and produced a 76-kDa form of PKC-alpha that lacked detectable 32P. The 76-kDa form was in the particulate rather than the cytosolic fraction, which suggests that it was produced from activated kinase. Alkaline phosphatase treatment of immunoprecipitated PKC-alpha converted the 80-kDa form to 76 kDa, but it had no effect on the mobility of the 76-kDa form, suggesting that it was not phosphorylated. Pulse-chase labeling of PKC-alpha with [35S]Met/Cys indicated that there is a precursor-product relationship between the 80- and 76-kDa forms, respectively. Inhibition of protein synthesis had no effect on the production of 76-kDa PKC-alpha by Bryo. PMA also produced 76-kDa PKC-alpha but was less potent and efficacious than Bryo. Bryo produced a more rapid loss of 80-kDa PKC-alpha protein and total Ca(2+)- and phospholipid-dependent PKC activity than PMA. The 76-kDa form is inactive and incompetent because it lacked detectable 32P under conditions that strongly autophosphorylated the 80-kDa form. We suggest that dephosphorylation predisposes PKC to proteolysis, and greater production of the 76-kDa form explains the more efficient downregulation of the kinase by Bryo vs. PMA.

Rapid response of protein synthesis to insulin in 3T3 cells: Effects of protein kinase C depletion and differences from the response to serum repletion

1986 ◽  
Vol 6 (9) ◽  
pp. 797-804 ◽  
Author(s):  
John E. Hesketh ◽  
Gillian P. Campbell ◽  
Peter J. Reeds
Keyword(s):  
Protein Synthesis ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Phorbol Ester ◽  
Actinomycin D ◽  
Calf Serum ◽  
Cell Protein ◽  
Foetal Calf Serum ◽  
3T3 Cells ◽  
Kinase C

Quiescent 3T3 cells grown in media containing 4% foetal calf serum showed different responses to insulin and to serum repletion (to 12%). Insulin stimulated protein synthesis within 1 h and this early response was insensitive to actinomycin D. The later insulin response showed progressive sensitivity to actinomycin D. The serum response was slower, not occurring until 1 h, and was inhibited by actinomycin D. Depletion of cell protein kinase C by pre-treatment with phorbol ester caused a total block of the immediate response to insulin but had little effect on the response to serum or the later response to insulin. Acute phorbol ester treatment stimulated protein synthesis.

scholarly journals Ribosomal RACK1:Protein Kinase C βII Modulates Intramolecular Interactions between Unstructured Regions of Eukaryotic Initiation Factor 4G (eIF4G) That Control eIF4E and eIF3 Binding

2018 ◽  
Vol 38 (19) ◽  
Author(s):  
Mikhail I. Dobrikov ◽  
Elena Y. Dobrikova ◽  
Matthias Gromeier
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Intramolecular Interactions ◽  
Initiation Factor ◽  
Binding Motif ◽  
Eukaryotic Initiation Factor ◽  
Kinase C ◽  
Eukaryotic Initiation Factor 4G ◽  
Β Sheet ◽  
Unstructured Regions

ABSTRACT The receptor for activated C kinase (RACK1), a conserved constituent of eukaryotic ribosomes, mediates phosphorylation of eukaryotic initiation factor 4G1(S1093) [eIF4G1(S1093)] and eIF3a(S1364) by protein kinase C βII (PKCβII) (M. I. Dobrikov, E. Y. Dobrikova, and M. Gromeier, Mol Cell Biol 38:e00304-18, 2018, https://doi.org/10.1128/MCB.00304-18). RACK1:PKCβII activation drives a phorbol ester-induced surge of global protein synthesis and template-specific translation induction of PKC–Raf–extracellular signal-regulated kinase 1/2 (ERK1/2)-responsive genes. For unraveling mechanisms of RACK1:PKCβII-mediated translation stimulation, we used sequentially truncated eIF4G1 in coimmunoprecipitation analyses to delineate a set of autoinhibitory elements in the N-terminal unstructured region (surrounding the eIF4E-binding motif) and the interdomain linker (within the eIF3-binding site) of eIF4G1. Computer-based predictions of secondary structure, mutational analyses, and fluorescent titration with the β-sheet dye thioflavin T suggest that eIF4G1(S1093) modulates a 4-stranded β-sheet composed of antiparallel β-hairpins formed by the autoinhibitory elements in eIF4G1's unstructured regions. The intact β-sheet “locks” the eIF4G configuration, preventing assembly with eIF3/40S ribosomal subunits. Upon PKC stimulation, activated RACK1:PKCβII phosphorylates eIF4G(S1093) in the tight 48S initiation complex, possibly facilitating dissociation/recycling of eIF4F.

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).

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