Related Experiment Video

Updated: Aug 14, 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

Phosphoinositide 3-kinase: from viral oncoprotein to drug target

Peter K Vogt1, Andreas G Bader, Sohye Kang

  • 1Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road BCC 239, La Jolla, CA 92037, USA. pkvogt@scripps.edu

Virology
|December 21, 2005
PubMed

Insights

Common PI3K mutations in cancer are oncogenic, activating Akt signaling. These mutated p110alpha proteins are promising drug targets for developing targeted cancer therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The catalytic subunit p110alpha of phosphoinositide 3-kinase (PI3K) and Akt are implicated as retroviral oncoproteins.
  • PI3K mutations are frequently observed in human cancers.
  • Retroviral vector technologies are being adapted to study PI3K mutations.

Purpose of the Study:

  • To investigate the oncogenic potential of frequently occurring p110alpha PI3K mutants.
  • To determine if these mutants activate Akt signaling and exhibit rapamycin sensitivity.
  • To establish mutated p110alpha as a viable drug target for cancer therapy.

Main Methods:

  • In vitro and in vivo assays to assess oncogenic transformation.
  • Enzymatic activity assays for p110alpha mutants.
  • Analysis of Akt activation pathways.
  • Evaluation of rapamycin sensitivity.

Main Results:

  • Frequently occurring p110alpha mutants demonstrate oncogenic properties in vitro and in vivo.
  • Mutant p110alpha exhibits enhanced enzymatic function and activates Akt.
  • The oncogenic activity of these mutants is sensitive to rapamycin.
  • Wild-type p110beta, gamma, and delta isoforms also induce oncogenic transformation.

Conclusions:

  • Mutated p110alpha proteins represent ideal drug targets due to their oncogenic gain-of-function.
  • Developing specific small molecule inhibitors for these mutant proteins is a realistic and urgent goal for cancer treatment.

More Related Videos

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...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
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...
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...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include: