Related Experiment Video

Updated: May 28, 2026

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry
08:07

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

Published on: July 26, 2019

Structural basis for activation and inhibition of class I phosphoinositide 3-kinases

Oscar Vadas1, John E Burke, Xuxiao Zhang

  • 1Laboratory of Molecular Biology, Medical Research Council, Hills Road, Cambridge CB20QH, UK. ovadas@mrc-lmb.cam.ac.uk

Science Signaling
|October 20, 2011
PubMed

Insights

Phosphoinositide 3-kinases (PI3Ks) regulate cell growth and metabolism. Understanding PI3K regulation and interactions is crucial for developing targeted cancer therapies.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Phosphoinositide 3-kinases (PI3Ks) are critical enzymes involved in numerous cellular processes, including growth, proliferation, and metabolism.
  • Aberrant PI3K activity, particularly class I PI3Ks, is frequently observed in human cancers, driving their development and progression.

Purpose of the Study:

  • To elucidate the regulatory mechanisms controlling PI3K activity.
  • To explore the role of PI3K partners in modulating signaling pathways.
  • To inform the development of isoform-specific PI3K inhibitors for cancer therapy.

Main Methods:

  • Review of existing literature on PI3K structure, function, and regulation.
  • Analysis of protein-protein interactions involving PI3K and its regulators.
  • Examination of structural data for PI3K complexes.

Main Results:

  • PI3Ks are heterodimers where catalytic subunit activity is controlled by regulatory subunits (e.g., p85).
  • Functional outcomes are influenced by the specific catalytic subunit isotype.
  • Novel PI3K partners (PTEN, PKA, nonstructural protein 1) modulate PI3K signaling.
  • Interactions with regulators affect membrane affinity and catalytic rates.
  • Crystal structures reveal regulatory mechanisms and aid inhibitor design.

Conclusions:

  • PI3K regulation is complex, involving subunit interactions and numerous partners.
  • Understanding these interactions is key to targeting PI3K in cancer.
  • Structural insights facilitate the development of specific inhibitors for therapeutic intervention.

More Related Videos

A Liposome Membrane Permeability Assay for Investigating the Effects of Phosphatidylinositol Phosphate Groups on Membranotropic Action of Venom PLA210:31

A Liposome Membrane Permeability Assay for Investigating the Effects of Phosphatidylinositol Phosphate Groups on Membranotropic Action of Venom PLA2

Published on: September 26, 2025

PIP-on-a-chip: A Label-free Study of Protein-phosphoinositide Interactions10:58

PIP-on-a-chip: A Label-free Study of Protein-phosphoinositide Interactions

Published on: July 27, 2017

Related Concept Videos

Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

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...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

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...
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

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 produces two-second...
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...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...