Multidrug resistance protein 4 (MRP4/ABCC4): a versatile efflux transporter for drugs and signalling molecules.
Multidrug resistance protein (MRP) 4 is a member of the MRP/ABCC subfamily of ATP-binding cassette transporters, which are capable of pumping a wide variety of endogenous and xenobiotic organic anionic compounds out of the cell. In addition to its role in the body distribution and renal excretion of a wide variety of antiviral, cytostatic, antibiotic and cardiovascular drugs, MRP4/ABCC4 has the remarkable ability to transport molecules involved in cellular signalling. These molecules include cyclic nucleotides, eicosanoids, urate and conjugated steroids. The unique structure, regulation and dual localisation of MRP4 in polarised cells could be connected with a key function in cellular protection and extracellular signalling pathways. This review focuses on recent insights into the versatile transport function of MRP4 and its potential as a new therapeutic target to modulate various pathophysiological signalling processes.
Russel
Frans G M
FG
Department of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Molecular Life Sciences, Geert Grooteplein 26, 6525 GA, Nijmegen, The Netherlands. F.Russel@ncmls.ru.nl <F.Russel@ncmls.ru.nl>
Koenderink
Jan B
JB
Masereeuw
Rosalinde
R
D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D002450:Cell Communication; D000242:Cyclic AMP / Q000502:physiology; D006152:Cyclic GMP / Q000502:physiology; D015777:Eicosanoids / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction; D014527:Uric Acid / Q000378:metabolism
D000242:Cyclic AMP; D006152:Cyclic GMP; D015777:Eicosanoids; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D014527:Uric Acid; C073492:ABCC4 protein, human