Vinculin, VASP, and profilin are coordinately regulated during actin remodeling in epithelial cells, which requires de novo protein synthesis and protein kinase signal transduction pathways

2004 ◽  
Vol 200 (2) ◽  
pp. 277-290 ◽  
Author(s):  
Margaret P. Quinlan
Keyword(s):  
Signal Transduction ◽  
Protein Synthesis ◽  
Protein Kinase ◽  
Epithelial Cells ◽  
De Novo ◽  
Signal Transduction Pathways ◽  
Actin Remodeling ◽  
De Novo Protein Synthesis

scholarly journals Dissection of Autophagosome Biogenesis into Distinct Nucleation and Expansion Steps

2000 ◽  
Vol 151 (5) ◽  
pp. 1025-1034 ◽  
Author(s):  
Hagai Abeliovich ◽  
William A. Dunn ◽  
John Kim ◽  
Daniel J. Klionsky
Keyword(s):  
Signal Transduction ◽  
Protein Synthesis ◽  
Membrane Trafficking ◽  
De Novo ◽  
Alternative Hypothesis ◽  
Translational Machinery ◽  
Transduction Mechanism ◽  
Signal Transduction Mechanism ◽  
Signal Transduction Event ◽  
De Novo Protein Synthesis

Rapamycin, an antifungal macrolide antibiotic, mimics starvation conditions in Saccharomyces cerevisiae through activation of a general G0 program that includes widespread effects on translation and transcription. Macroautophagy, a catabolic membrane trafficking phenomenon, is a prominent part of this response. Two views of the induction of autophagy may be considered. In one, up-regulation of proteins involved in autophagy causes its induction, implying that autophagy is the result of a signal transduction mechanism leading from Tor to the transcriptional and translational machinery. An alternative hypothesis postulates the existence of a dedicated signal transduction mechanism that induces autophagy directly. We tested these possibilities by assaying the effects of cycloheximide and specific mutations on the induction of autophagy. We find that induction of autophagy takes place in the absence of de novo protein synthesis, including that of specific autophagy-related proteins that are up-regulated in response to rapamycin. We also find that dephosphorylation of Apg13p, a signal transduction event that correlates with the onset of autophagy, is also independent of new protein synthesis. Finally, our data indicate that autophagosomes that form in the absence of protein synthesis are significantly smaller than normal, indicating a role for de novo protein synthesis in the regulation of autophagosome expansion. Our results define the existence of a signal transduction-dependent nucleation step and a separate autophagosome expansion step that together coordinate autophagosome biogenesis.

scholarly journals De Novo Protein Synthesis by Bovine Uterine Tube (Oviduct) Epithelial Cells Changes during Co-Culture with Bull Spermatozoa1

1993 ◽  
Vol 48 (4) ◽  
pp. 851-856 ◽  
Author(s):  
J. E. Ellington ◽  
G. G. Ignotz ◽  
B. A. Ball ◽  
V. N. Meyers-Wallen ◽  
W. B. Currie
Keyword(s):  
Protein Synthesis ◽  
Epithelial Cells ◽  
De Novo ◽  
Uterine Tube ◽  
Oviduct Epithelial Cells ◽  
De Novo Protein Synthesis

scholarly journals GADD34-mediated dephosphorylation of eIF2α facilitates pseudorabies virus replication by maintaining de novo protein synthesis

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Ting Zhu ◽  
Xueli Jiang ◽  
Hangkuo Xin ◽  
Xiaohui Zheng ◽  
Xiaonuan Xue ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Protein Kinase ◽  
Pseudorabies Virus ◽  
De Novo ◽  
Initiation Factor ◽  
Protein Kinase R ◽  
Eif2α Phosphorylation ◽  
Phosphorylation Level ◽  
Global Protein Synthesis ◽  
De Novo Protein Synthesis

AbstractViruses have evolved multiple strategies to manipulate their host’s translational machinery for the synthesis of viral proteins. A common viral target is the alpha subunit of eukaryotic initiation factor 2 (eIF2α). In this study, we show that global protein synthesis was increased but the eIF2α phosphorylation level was markedly decreased in porcine kidney 15 (PK15) cells infected with pseudorabies virus (PRV), a swine herpesvirus. An increase in the eIF2α phosphorylation level by salubrinal treatment or transfection of constructs expressing wild-type eIF2α or an eIF2α phosphomimetic [eIF2α(S51D)] attenuated global protein synthesis and suppressed PRV replication. To explore the mechanism involved in the inhibition of eIF2α phosphorylation during PRV infection, we examined the phosphorylation status of protein kinase R-like endoplasmic reticulum kinase (PERK) and double-stranded RNA-dependent protein kinase R (PKR), two kinases that regulate eIF2α phosphorylation during infection with numerous viruses. We found that the level of neither phosphorylated (p)-PERK nor p-PKR was altered in PRV-infected cells or the lungs of infected mice. However, the expression of growth arrest and DNA damage-inducible protein 34 (GADD34), which promotes eIF2α dephosphorylation by recruiting protein phosphatase 1 (PP1), was significantly induced both in vivo and in vitro. Knockdown of GADD34 and inhibition of PP1 activity by okadaic acid treatment led to increased eIF2α phosphorylation but significantly suppressed global protein synthesis and inhibited PRV replication. Collectively, these results demonstrated that PRV induces GADD34 expression to promote eIF2α dephosphorylation, thereby maintaining de novo protein synthesis and facilitating viral replication.

Developmental decline in components of signal transduction pathways regulating protein synthesis in pig muscle

2002 ◽  
Vol 282 (3) ◽  
pp. E585-E592 ◽  
Author(s):  
Scot R. Kimball ◽  
Peter A. Farrell ◽  
Hahn V. Nguyen ◽  
Leonard S. Jefferson ◽  
Teresa A. Davis
Keyword(s):  
Signal Transduction ◽  
Protein Synthesis ◽  
Protein Kinase ◽  
Mammalian Target Of Rapamycin ◽  
Initiation Factor ◽  
Signal Transduction Pathways ◽  
Neonatal Pigs ◽  
Ribosomal Protein S6 ◽  
Pig Muscle ◽  
Signaling Components

Our previous studies showed that the feeding-induced stimulation of protein synthesis in skeletal muscle of neonatal pigs is accompanied by enhanced phosphorylation of the eukaryotic initiation factor (eIF)4E-binding protein (4E-BP1) and the ribosomal protein S6 kinase (S6K1). These effects of feeding are substantially reduced with development. The goal of the present investigation was to delineate the basis for the reduced responsiveness to feeding observed in the older animals. In these studies, the content and activity of protein kinases located upstream of S6K1 and 4E-BP1 in signal transduction pathways activated by amino acids, insulin, and insulin-like growth factor I were examined in 7- and 26-day-old pigs that were either fasted overnight or fed porcine milk after an overnight fast. Feeding stimulated phosphatidylinositol (PI) 3-kinase activity to the same extent in muscle of 7- and 26-day-old pigs, suggesting that PI 3-kinase is not limiting in muscle of older animals. In contrast, protein kinase B (PKB) activity was significantly less in muscle from 26- vs. 7-day-old pigs, regardless of nutritional status, suggesting that its activity is regulated by mechanisms distinct from PI 3-kinase. In part, the reduced PKB responsiveness can be attributed to a developmental decline in PKB content. Likewise, muscle content of the protein kinase termed mammalian target of rapamycin (mTOR) in 26-day-old pigs was <25% of that in 7-day-old animals. Finally, in agreement with our earlier work showing that S6K1 phosphorylation is reduced in older animals, S6K1 activity was stimulated to a lesser extent in 26- compared with 7-day-old pigs. Overall, the results suggest that the blunted protein synthetic response observed in 26- vs. 7-day-old neonatal pigs is due in part to decreased content and/or activity of signaling components downstream of PI 3-kinase, e.g., PKB, mTOR, and S6K1.

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