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Updated: Jun 6, 2026

Identification of Kinase-substrate Pairs Using High Throughput Screening
Published on: August 29, 2015
Regulation of ABC transporter function via phosphorylation by protein kinases
Elzbieta I Stolarczyk1, Cassandra J Reiling, Christian M Paumi
1Department of Toxicology, University of Kentucky, Lexington, KY, USA.
Abstract:
ATP-binding cassette (ABC) transporters are multispanning membrane proteins that utilize ATP to move a broad range of substrates across cellular membranes. ABC transporters are involved in a number of human disorders and diseases. Overexpression of a subset of the transporters has been closely linked to multidrug resistance in both bacteria and viruses and in cancer. A poorly understood and important aspect of ABC transporter biology is the role of phosphorylation as a mechanism to regulate transporter function. In this review, we summarize the current literature addressing the role of phosphorylation in regulating ABC transporter function. A comprehensive list of all the phosphorylation sites that have been identified for the human ABC transporters is presented, and we discuss the role of individual kinases in regulating transporter function. We address the potential pitfalls and difficulties associated with identifying phosphorylation sites and the corresponding kinase(s), and we discuss novel techniques that may circumvent these problems. We conclude by providing a brief perspective on studying ABC transporter phosphorylation.
Insights
Phosphorylation regulates ATP-binding cassette (ABC) transporter function, impacting diseases and drug resistance. This review details human ABC transporter phosphorylation sites and kinases, aiding future research.
Area of Science:
- Biochemistry and Molecular Biology
- Cellular Transport Mechanisms
Background:
- ATP-binding cassette (ABC) transporters are crucial membrane proteins facilitating substrate transport via ATP hydrolysis.
- Dysregulation of ABC transporters is implicated in human diseases, including multidrug resistance in cancer, bacteria, and viruses.
- The role of phosphorylation in modulating ABC transporter activity remains an area requiring further elucidation.
Purpose of the Study:
- To review the current literature on the function of phosphorylation in regulating ABC transporter activity.
- To present a comprehensive list of identified phosphorylation sites in human ABC transporters.
- To discuss the involvement of specific kinases and challenges in studying ABC transporter phosphorylation.
Main Methods:
- Literature review of studies investigating ABC transporter phosphorylation.
- Compilation of identified phosphorylation sites across human ABC transporter family members.
- Analysis of kinase-substrate interactions and regulatory roles.
Main Results:
- Detailed summary of known phosphorylation sites and their regulatory impact on ABC transporter function.
- Identification of key kinases involved in phosphorylating human ABC transporters.
- Discussion of technical challenges and novel approaches for site and kinase identification.
Conclusions:
- Phosphorylation is a critical regulatory mechanism for ABC transporter function.
- Understanding these phosphorylation events is vital for therapeutic strategies against ABC transporter-related diseases.
- Future research should focus on advanced techniques to overcome current limitations in studying ABC transporter phosphorylation.
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