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Related Concept Videos

Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
ATP Synthase: Structure01:18

ATP Synthase: Structure

ATP synthase or ATPase is among the most conserved proteins found in bacteria, mammals, and plants. This enzyme can catalyze a forward reaction in response to the electrochemical gradient, producing ATP from ADP and inorganic phosphate. ATP synthase can also work in a reverse direction by hydrolyzing ATP and generating an electrochemical gradient. Different forms of ATP synthases have evolved special features to meet the specific demands of the cell. Based on their specific feature, ATP...
ATP Synthase: Mechanism01:48

ATP Synthase: Mechanism

In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased ATP...
Phosphorylation01:02

Phosphorylation

The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
The ADP/ATP Carrier Protein01:42

The ADP/ATP Carrier Protein

ADP/ATP carrier or AAC protein is the most abundant carrier protein in the inner mitochondrial membrane. It transports large quantities of ADP and ATP, equivalent to the average human body weight, every day. Among other transporters, ACC protein is one of the best-studied members of the mitochondrial carrier protein family. The ADP/ATP carrier protein comprises two transmembrane helices connected to a loop and a single alpha-helix on the matrix side. It switches between two conformational...

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Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
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The eIF2α kinases: their structures and functions.

Neysan Donnelly1, Adrienne M Gorman, Sanjeev Gupta

  • 1Apoptosis Research Center, National University of Ireland, Galway, Ireland.

Cellular and Molecular Life Sciences : CMLS
|January 29, 2013
PubMed
Summary
This summary is machine-generated.

Cellular stress triggers eIF2α phosphorylation by four kinases, reducing protein synthesis. This integrated stress response (ISR) aims to restore homeostasis but can also lead to apoptosis, influencing cell fate.

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Area of Science:

  • Molecular Biology
  • Cellular Stress Response
  • Signal Transduction

Background:

  • Cellular stress signals converge on eIF2α phosphorylation, a key event regulating protein synthesis.
  • This phosphorylation is mediated by four distinct kinases: PERK, PKR, GCN2, and HRI, each responding to specific stress types.
  • eIF2α phosphorylation significantly reduces global protein synthesis, acting as a protective cellular mechanism.

Purpose of the Study:

  • To review the structure, activation mechanisms, and functions of the four eIF2α kinases.
  • To elucidate how kinase structure dictates their specific stress responses and regulatory pathways.
  • To discuss the dual role of eIF2α kinase activation in promoting cellular homeostasis via the ISR and potentially inducing apoptosis.

Main Methods:

  • Review of existing literature on eIF2α kinases, their structures, and activation.
  • Analysis of the signaling pathways involved in the integrated stress response (ISR).
  • Discussion of the interplay between kinase activity, translational control, and cell fate determination.

Main Results:

  • Four kinases (PERK, PKR, GCN2, HRI) phosphorylate eIF2α at serine 51 in response to diverse stresses.
  • While sharing kinase domain similarity, each kinase possesses unique regulatory features determining its activation.
  • eIF2α kinase activation leads to general translational attenuation and enhanced translation of specific mRNAs like ATF4, initiating the ISR.
  • The ISR aims to resolve stress and restore cellular balance, but under certain conditions, translational attenuation can promote apoptosis.

Conclusions:

  • The four eIF2α kinases are crucial regulators of cellular response to stress, with distinct activation specificities.
  • Understanding kinase structure-function relationships is key to comprehending cellular stress management.
  • The eIF2α-P-eIF2-ATF4 pathway (ISR) is a central hub balancing cell survival and death decisions.