Conclusion
Our data demonstrate that inhibition of protein tyrosine phosphatases down-regulates ABCA1 expression, indicating a new level of regulation of a key protein in cholesterol export.
Objective
ATP-binding cassette transporter (ABC)-A1 is an important protein of cholesterol homoeostasis and atherosclerosis as it is the major lipid transporter responsible for the export of cholesterol from cells. Many studies have examined kinase regulation of ABCA1 expression. In contrast, very little is known about whether dephosphorylation events play a role in ABCA1 expression. In this study, we explored the involvement of phosphatases in the regulation of ABCA1 expression.
Results
We observed that general protein tyrosine phosphatase inhibitors ablated ABCA1 protein and mRNA when stimulated with synthetic ligands. This effect is transcriptional, and appears to involve the nuclear receptor, retinoid X receptor (RXR).