Regulation of ABC Transporter Function Via Phosphorylation by Protein Kinases

Elzbieta      I. Stolarczyk; Cassandra      J. Reiling; Christian      M. Paumi

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 [1]. 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.

Keywords: ABC transporter, CK2, kinase, LC/MS, PKA, PKC, phosphorylation, regulation, multispanning membrane proteins, multidrug resistance, cancer, corresponding kinase(s), circumvent, post-translational regulation