Related Experiment Video

Updated: May 30, 2026

A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors
10:17

A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors

Published on: April 29, 2022

Using tandem mass spectrometry in targeted mode to identify activators of class IA PI3K in cancer

Xuemei Yang1, Alexa B Turke, Jie Qi

  • 1Beth Israel Deaconess Medical Center, Division of Signal Transduction, Boston, Massachusetts 02115, USA.

Cancer Research
|July 22, 2011
PubMed

Insights

A new mass spectrometry method identifies upstream activators of Phosphatidylinositol-3-kinase (PI3K) in cancer. This approach guides personalized tyrosine kinase inhibitor (TKI) therapy selection for improved patient outcomes.

Area of Science:

  • Oncology
  • Biochemistry
  • Analytical Chemistry

Background:

  • Phosphatidylinositol-3-kinase (PI3K) is frequently activated in cancers, either by direct mutation or via upstream receptor tyrosine kinases (TKs).
  • Current methods lack systematic approaches to identify specific TK signaling pathways activating PI3K in individual cancers.
  • Identifying these pathways is crucial for selecting effective tyrosine kinase inhibitor (TKI) drugs in personalized cancer therapy.

Purpose of the Study:

  • To develop and validate a quantitative mass spectrometry-based approach for identifying upstream activators of PI3K.
  • To demonstrate the utility of this method in guiding TKI selection for personalized cancer treatment.

Main Methods:

  • Quantitative liquid chromatography tandem mass spectrometry (LC-MS/MS) was employed to identify and quantify PI3K activators.
  • The approach was applied to non-small cell lung carcinoma and breast cancer models.
  • Functional interactions governing PI3K regulation were assessed in vitro and in vivo.

Main Results:

  • The method successfully identified mechanisms of PI3K activation in non-small cell lung carcinoma models, enabling appropriate TKI selection.
  • Molecular mechanisms and adaptors involved in PI3K activation after mTORC1 inhibition were elucidated.
  • The approach quantitatively measured a PIK3CA helical domain mutant (E545K) associated with PI3K activation in breast cancer cells.

Conclusions:

  • A robust mass spectrometry-based strategy has been established for identifying functional interactions regulating PI3K in cancer.
  • This technique provides a means to define PI3K-activating pathways in specific tumors.
  • The findings support the use of this approach to inform clinical decision-making and personalize cancer therapy.

More Related Videos

Quantitative Mass Spectrometric Profiling of Cancer-cell Proteomes Derived From Liquid and Solid Tumors08:08

Quantitative Mass Spectrometric Profiling of Cancer-cell Proteomes Derived From Liquid and Solid Tumors

Published on: February 27, 2015

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays07:42

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays

Published on: September 19, 2018

Related Concept Videos

Tandem Mass Spectrometry01:21

Tandem Mass Spectrometry

Tandem mass spectrometry is a technique that uses multiple mass analyzers in series to obtain a higher selectivity and reduce chemical noise during analyte detection. Instruments with multiple analyzers separated by an interaction cell enable secondary fragmentation and selected study of the fragment ions.Secondary fragmentations occur in the interaction cell and can be induced by various factors. Fragmentation induced by collision with inert gases, such as N2, Ar, He, etc., is called...
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...
Peptide Identification Using Tandem Mass Spectrometry01:33

Peptide Identification Using Tandem Mass Spectrometry

Tandem mass spectrometry, also known as MS/MS or MS2, is an analytical technique that employs two mass analyzers. Essentially it is a series of mass spectrometers that helps isolate a particular biomolecule and then helps study its chemical properties.
This technique helps gather information regarding the protein from which the peptide was obtained and to study the peptides’ amino acid sequence. Identifying peptides from a complex mixture is an important component of the growing field of...
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...