Related Experiment Video
Updated: Sep 3, 2025
13:22
Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays
Published on: October 23, 2019
8.0K
KOPI: Kinase inhibitOr Proteome Impact analysis
Ginny Xiaohe Li1,2, Tianyun Zhao3,4, Loo Chien Wang3
1Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Scientific Reports
|July 29, 2022
Summary
We developed a new workflow, kinase inhibitor proteome impact analysis (KOPI), for rapid proteomic assessment of drug effects. KOPI identified novel staurosporine interactions and revealed its paradoxical phosphorylation patterns.
Area of Science:
- Proteomics
- Pharmacology
- Cell Biology
Background:
- Kinase inhibitors can have unintended on/off-target effects impacting the proteome.
- Assessing these proteomic effects requires efficient and rapid analytical methods.
Purpose of the Study:
- To develop and validate a workflow for rapid proteomic assessment of kinase inhibitor effects.
- To characterize the impact of staurosporine on the K562 cell proteome using the developed workflow.
Main Methods:
- Development of the kinase inhibitor proteome impact analysis (KOPI) workflow.
- Application of KOPI to analyze the proteome of K562 cells treated with staurosporine (STS).
- Mass spectrometry-based proteomics for comprehensive proteome profiling.
Main Results:
- The KOPI workflow enabled rapid proteomic assessment of staurosporine's effects.
- Systematic identification of staurosporine's non-kinome protein interactors.
- Discovery of paradoxical hyper- and biphasic phosphorylation patterns induced by staurosporine.
Conclusions:
- The KOPI workflow is effective for rapid and comprehensive proteomic analysis of kinase inhibitors.
- Staurosporine exhibits previously unrecognized off-target interactions and complex phosphorylation effects.
- This approach aids in understanding drug mechanisms and potential toxicities.
More Related Videos
Related Concept Videos
02:54Protein Kinases and Phosphatases
13.3K
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
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
13.3K
02:04Protein-protein Interfaces
12.8K
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...
12.8K
01:22PI3K/mTOR/AKT Signaling Pathway
3.9K
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...
3.9K
02:26Protein Networks
4.1K
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
4.1K
01:33Proteomics
7.8K
A proteome is the entire set of proteins that a cell type produces. We can study proteomes using the knowledge of genomes because genes code for mRNAs, and the mRNAs encode proteins. Although mRNA analysis is a step in the right direction, not all mRNAs are translated into proteins.
Proteomics is the study of proteomes' function. It involves the large-scale systematic study of the proteome to denote the protein complement expressed by a genome. Scientist Mark Wilkins coined the term...
Proteomics is the study of proteomes' function. It involves the large-scale systematic study of the proteome to denote the protein complement expressed by a genome. Scientist Mark Wilkins coined the term...
7.8K
01:22Amplifying Signals via Enzymatic Cascade
8.7K
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...
8.7K