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Related Concept Videos

Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

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Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
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Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

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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...
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Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

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The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

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Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
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IP3/DAG Signaling Pathway01:11

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Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
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Phosphorylation01:02

Phosphorylation

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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.
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Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry
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Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry

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Phosphatidylinositol 4-kinases: Function, structure, and inhibition.

Evzen Boura1, Radim Nencka1

  • 1Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i, Gilead Sciences & IOCB Research Centre, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic.

Experimental Cell Research
|July 18, 2015
PubMed
Summary

Phosphatidylinositol 4-kinases (PI4Ks) create PI4P, essential for Golgi function and viral replication. Inhibitors targeting PI4Ks show promise as antiviral therapies by disrupting viral processes.

Keywords:
Crystal structureInhibitorPhosphatidylinositol 4-kinaseVirus

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Radiolabeling and Quantification of Cellular Levels of Phosphoinositides by High Performance Liquid Chromatography-coupled Flow Scintillation
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Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry
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Radiolabeling and Quantification of Cellular Levels of Phosphoinositides by High Performance Liquid Chromatography-coupled Flow Scintillation
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Absolute Quantitation of Inositol Pyrophosphates by Capillary Electrophoresis Electrospray Ionization Mass Spectrometry
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Area of Science:

  • Biochemistry
  • Cell Biology
  • Virology

Background:

  • Phosphatidylinositol 4-kinases (PI4Ks) synthesize phosphatidylinositol 4-phosphate (PI4P), a crucial phosphoinositide.
  • PI4P regulates membrane trafficking at the Golgi and trans-Golgi network (TGN).
  • Human PI4Ks include two type II (α, β) and two type III (α, β) enzymes.

Purpose of the Study:

  • To review the structure and function of PI4Ks.
  • To explore the role of PI4Ks in viral replication.
  • To discuss the therapeutic potential of PI4K inhibitors in human medicine.

Main Methods:

  • Analysis of recently solved crystal structures of PI4K types II and III.
  • Review of literature on PI4K function in cellular processes and viral hijacking.
  • Discussion of PI4K inhibitor development for antiviral applications.

Main Results:

  • Crystal structures reveal atomic details of PI4K function.
  • +RNA viruses hijack type III PI4Ks to form replication-supporting membranous webs.
  • Selective PI4K inhibitors are being developed as antiviral agents.

Conclusions:

  • PI4Ks are critical enzymes with significant roles in cellular trafficking and viral pathogenesis.
  • Understanding PI4K structure and function is key to developing novel antiviral strategies.
  • Targeting PI4Ks offers a promising avenue for therapeutic intervention against viral infections.