Abcc4

Summary

Gene Symbol: Abcc4
Description: ATP-binding cassette, sub-family C (CFTR/MRP), member 4
Alias: ABCC4-N1, D630049P08Rik, MOATB, MRP4, multidrug resistance-associated protein 4
Species: mouse
Products:     Abcc4

Top Publications

  1. Hara Y, Sassi Y, Guibert C, Gambaryan N, Dorfmuller P, Eddahibi S, et al. Inhibition of MRP4 prevents and reverses pulmonary hypertension in mice. J Clin Invest. 2011;121:2888-97 pubmed publisher
    Multidrug resistance-associated protein 4 (MRP4, also known as Abcc4) regulates intracellular levels of cAMP and cGMP in arterial SMCs...
  2. van de Ven R, de Groot J, Reurs A, Wijnands P, van de Wetering K, Schuetz J, et al. Unimpaired immune functions in the absence of Mrp4 (Abcc4). Immunol Lett. 2009;124:81-7 pubmed publisher
    ..we reported that the human ATP-binding cassette (ABC) transporter multidrug resistance protein 4 (MRP4 and ABCC4) is required for the migration of human DC...
  3. Belinsky M, Guo P, Lee K, Zhou F, Kotova E, Grinberg A, et al. Multidrug resistance protein 4 protects bone marrow, thymus, spleen, and intestine from nucleotide analogue-induced damage. Cancer Res. 2007;67:262-8 pubmed
    ..However, the in vivo pharmacologic functions of the pump are largely unexplored. Here, using Mrp4(-/-) mice as a model system, and the nucleotide analogue, 9'-(2'-phosphonylmethoxyethyl)-adenine (PMEA) as a probe, ..
  4. Takenaka K, Morgan J, Scheffer G, Adachi M, Stewart C, Sun D, et al. Substrate overlap between Mrp4 and Abcg2/Bcrp affects purine analogue drug cytotoxicity and tissue distribution. Cancer Res. 2007;67:6965-72 pubmed
    ..analogue, 9-(2-(phosphonomethoxy)ethyl)-adenine (PMEA), and up-regulation of Abcg2 in some tissues of the Mrp4 KO mouse prompted us to evaluate the possibility that Abcg2 might transport purine-derived drugs...
  5. De Wolf C, Yamaguchi H, van der Heijden I, Wielinga P, Hundscheid S, Ono N, et al. cGMP transport by vesicles from human and mouse erythrocytes. FEBS J. 2007;274:439-50 pubmed
    cGMP secretion from cells can be mediated by ATP-binding cassette (ABC) transporters ABCC4, ABCC5, and ABCC11. Indirect evidence suggests that ABCC4 and ABCC5 contribute to cGMP transport by erythrocytes...
  6. Leggas M, Adachi M, Scheffer G, Sun D, Wielinga P, Du G, et al. Mrp4 confers resistance to topotecan and protects the brain from chemotherapy. Mol Cell Biol. 2004;24:7612-21 pubmed
    The role of the multidrug resistance protein MRP4/ABCC4 in vivo remains undefined. To explore this role, we generated Mrp4-deficient mice...
  7. Imaoka T, Kusuhara H, Adachi M, Schuetz J, Takeuchi K, Sugiyama Y. Functional involvement of multidrug resistance-associated protein 4 (MRP4/ABCC4) in the renal elimination of the antiviral drugs adefovir and tenofovir. Mol Pharmacol. 2007;71:619-27 pubmed
    ..In this study, we examined the involvement of multidrug resistance-associated protein (MRP)4 (ABCC4) in their luminal efflux in the kidney...
  8. Paek H, Antoine M, Diaz F, Hebert J. Increased ?-catenin activity in the anterior neural plate induces ectopic mid-hindbrain characteristics. Dev Dyn. 2012;241:242-6 pubmed publisher
  9. Lien L, Chen Z, Chung C, Yen T, Chiu H, Chou D, et al. Multidrug resistance protein 4 (MRP4/ABCC4) regulates thrombus formation in vitro and in vivo. Eur J Pharmacol. 2014;737:159-67 pubmed publisher
    The multidrug resistance protein 4 (MRP4) is a member of the ABCC subfamily of the adenosine triphosphate-binding cassette transporters that remove cyclic nucleotides from platelets and uptake ADP into dense granule in platelets...

More Information

Publications48

  1. Vasilyeva A, Durmus S, Li L, Wagenaar E, Hu S, Gibson A, et al. Hepatocellular Shuttling and Recirculation of Sorafenib-Glucuronide Is Dependent on Abcc2, Abcc3, and Oatp1a/1b. Cancer Res. 2015;75:2729-36 pubmed publisher
  2. Stedman C, Liddle C, Coulter S, Sonoda J, Alvarez J, Evans R, et al. Benefit of farnesoid X receptor inhibition in obstructive cholestasis. Proc Natl Acad Sci U S A. 2006;103:11323-8 pubmed
    ..the lowering of bile acid concentrations and altered expression of the hepatic transporters Mdr1, Mdr2, BSEP, and Mrp4. FXR KO mice also exhibit a biphasic lipid profile after bile duct ligation, with an increase in high-density ..
  3. Sinha C, Ren A, Arora K, Moon C, Yarlagadda S, Woodrooffe K, et al. PKA and actin play critical roles as downstream effectors in MRP4-mediated regulation of fibroblast migration. Cell Signal. 2015;27:1345-55 pubmed publisher
    Multidrug resistance protein 4 (MRP4), a member of the ATP binding cassette transporter family, functions as a plasma membrane exporter of cyclic nucleotides...
  4. van de Wetering K, Zelcer N, Kuil A, Feddema W, Hillebrand M, Vlaming M, et al. Multidrug resistance proteins 2 and 3 provide alternative routes for hepatic excretion of morphine-glucuronides. Mol Pharmacol. 2007;72:387-94 pubmed
    ..Our results show that murine Mrp2 and Mrp3 provide alternative routes for the excretion of a glucuronidated substrate from the liver in vivo. ..
  5. de Waart D, van de Wetering K, Kunne C, Duijst S, Paulusma C, Oude Elferink R. Oral availability of cefadroxil depends on ABCC3 and ABCC4. Drug Metab Dispos. 2012;40:515-21 pubmed publisher
    ..We have tested whether ATP-binding cassette (ABC) transporters ABCC3 and/or ABCC4 are involved in the latter process...
  6. Marquez B, Ameye G, Vallet C, Tulkens P, Poirel H, Van Bambeke F. Characterization of Abcc4 gene amplification in stepwise-selected mouse J774 macrophages resistant to the topoisomerase II inhibitor ciprofloxacin. PLoS ONE. 2011;6:e28368 pubmed publisher
    ..inhibiting bacterial topoisomerases, selects for resistant cells that overexpress the efflux transporter Abcc4 (Marquez et al. [2009] Antimicrob. Agents Chemother...
  7. Decouture B, Dreano E, Belleville Rolland T, Kuci O, Dizier B, Bazaa A, et al. Impaired platelet activation and cAMP homeostasis in MRP4-deficient mice. Blood. 2015;126:1823-30 pubmed publisher
    ..In this study, we evaluated the role of multidrug resistance protein 4 (MRP4, or ABCC4), a nucleotide transporter, in platelet functions in vivo and in vitro by investigating MRP4-deficient mice...
  8. Furmanski B, Hu S, Fujita K, Li L, Gibson A, Janke L, et al. Contribution of ABCC4-mediated gastric transport to the absorption and efficacy of dasatinib. Clin Cancer Res. 2013;19:4359-4370 pubmed publisher
    Several oral multikinase inhibitors are known to interact in vitro with the human ATP-binding cassette transporter ABCC4 (MRP4), but the in vivo relevance of this interaction remains poorly understood...
  9. Schymeinsky J, Mayer H, Tomsic C, Tilp C, Schuetz J, Cui Y, et al. The absence of mrp4 has no effect on the recruitment of neutrophils and eosinophils into the lung after LPS, cigarette smoke or allergen challenge. PLoS ONE. 2013;8:e61193 pubmed publisher
    The multidrug resistance protein 4 (Mrp4) is an ATP-binding cassette transporter that is capable of exporting the second messenger cAMP from cells, a process that might regulate cAMP-mediated anti-inflammatory processes...
  10. Rehman S, Ishqi H, Husain M, Sarwar T, Tabish M. A novel exon generates ubiquitously expressed alternatively spliced new transcript of mouse Abcc4 gene. Gene. 2016;594:131-137 pubmed publisher
    b>Abcc4 gene codes for a protein (ABCC4) involved in the transportation of different classes of drugs outside the cells...
  11. Sinha C, Ren A, Arora K, Moon C, Yarlagadda S, Zhang W, et al. Multi-drug resistance protein 4 (MRP4)-mediated regulation of fibroblast cell migration reflects a dichotomous role of intracellular cyclic nucleotides. J Biol Chem. 2013;288:3786-94 pubmed publisher
    ..In this study, we used multidrug resistance protein 4 (MRP4)-expressing cell lines and MRP4 knock-out mice as model systems and wound healing assays as the experimental system ..
  12. Renga B, Migliorati M, Mencarelli A, Cipriani S, D Amore C, Distrutti E, et al. Farnesoid X receptor suppresses constitutive androstane receptor activity at the multidrug resistance protein-4 promoter. Biochim Biophys Acta. 2011;1809:157-65 pubmed publisher
    Multidrug resistance protein-4 (MRP4) is a member of the multidrug resistance associated gene family that is expressed on the basolateral membrane of hepatocytes and undergoes adaptive up-regulation in response to cholestatic injury or ..
  13. Jin D, Ni T, Sun J, Wan H, Amack J, Yu G, et al. Prostaglandin signalling regulates ciliogenesis by modulating intraflagellar transport. Nat Cell Biol. 2014;16:841-51 pubmed publisher
    ..leakytail (lkt) mutants show ciliogenesis defects, and the lkt locus encodes an ATP-binding cassette transporter (ABCC4)...
  14. Rius M, Nies A, Hummel Eisenbeiss J, Jedlitschky G, Keppler D. Cotransport of reduced glutathione with bile salts by MRP4 (ABCC4) localized to the basolateral hepatocyte membrane. Hepatology. 2003;38:374-84 pubmed
    ..In this study we have localized the multidrug resistance protein 4 (MRP4; ABCC4) to the basolateral membrane of human, rat, and mouse hepatocytes and human hepatoma HepG2 cells...
  15. Morgan J, Cheepala S, Wang Y, Neale G, Adachi M, Nachagari D, et al. Deregulated hepatic metabolism exacerbates impaired testosterone production in Mrp4-deficient mice. J Biol Chem. 2012;287:14456-66 pubmed publisher
    The physiological role of multidrug resistance protein 4 (Mrp4, Abcc4) in the testes is unknown...
  16. Cheepala S, Pitre A, Fukuda Y, Takenaka K, Zhang Y, Wang Y, et al. The ABCC4 membrane transporter modulates platelet aggregation. Blood. 2015;126:2307-19 pubmed publisher
    ..Previous studies have suggested that the ATP-binding cassette (ABC) transporter, ABCC4, functions in platelet-dense granules...
  17. Tagen M, Zhuang Y, Zhang F, Harstead K, Shen J, Schaiquevich P, et al. P-glycoprotein, but not multidrug resistance protein 4, plays a role in the systemic clearance of irinotecan and SN-38 in mice. Drug Metab Lett. 2010;4:195-201 pubmed
    The ATP-binding cassette transporters P-glycoprotein (ABCB1, MDR1) and multidrug resistance protein 4 (MRP4) efflux irinotecan and its active metabolite SN-38 in vitro, and thus may contribute to system clearance of these compounds...
  18. Chapy H, Saubaméa B, Tournier N, Bourasset F, Behar Cohen F, Declèves X, et al. Blood-brain and retinal barriers show dissimilar ABC transporter impacts and concealed effect of P-glycoprotein on a novel verapamil influx carrier. Br J Pharmacol. 2016;173:497-510 pubmed publisher
    ..P-gp, Bcrp, Mrp1 and Mrp4 were studied by confocal retina imaging...
  19. Drenberg C, Hu S, Li L, Buelow D, Orwick S, Gibson A, et al. ABCC4 Is a Determinant of Cytarabine-Induced Cytotoxicity and Myelosuppression. Clin Transl Sci. 2016;9:51-9 pubmed publisher
    ..Based on previous studies implicating ABCC4/MRP4 in the transport of nucleosides, we hypothesized that cytarabine is sensitive to ABCC4-mediated efflux, ..
  20. Assem M, Schuetz E, Leggas M, Sun D, Yasuda K, Reid G, et al. Interactions between hepatic Mrp4 and Sult2a as revealed by the constitutive androstane receptor and Mrp4 knockout mice. J Biol Chem. 2004;279:22250-7 pubmed
    The ABC transporter, Mrp4, transports the sulfated steroid DHEA-s, and sulfated bile acids interact with Mrp4 with high affinity. Hepatic Mrp4 levels are low, but increase under cholestatic conditions...
  21. Sassi Y, Ahles A, Truong D, Baqi Y, Lee S, Husse B, et al. Cardiac myocyte-secreted cAMP exerts paracrine action via adenosine receptor activation. J Clin Invest. 2014;124:5385-97 pubmed publisher
    ..primary cells and in myocardial tissue from murine hearts revealed that cardiomyocytes depend on the transporter ABCC4 to export cAMP as an extracellular signal...
  22. Zamek Gliszczynski M, Nezasa K, Tian X, Bridges A, Lee K, Belinsky M, et al. Evaluation of the role of multidrug resistance-associated protein (Mrp) 3 and Mrp4 in hepatic basolateral excretion of sulfate and glucuronide metabolites of acetaminophen, 4-methylumbelliferone, and harmol in Abcc3-/- and Abcc4-/- mice. J Pharmacol Exp Ther. 2006;319:1485-91 pubmed
    ..of the glucuronide and sulfate metabolites of acetaminophen, 4-methylumbelliferone, and harmol in Abcc3(-/-) and Abcc4(-/-) mice using a cassette dosing approach...
  23. Maeng H, Lee W, Jin Q, Chang J, Shim W. Upregulation of COX-2 in the lung cancer promotes overexpression of multidrug resistance protein 4 (MRP4) via PGE2-dependent pathway. Eur J Pharm Sci. 2014;62:189-96 pubmed publisher
    ..Here, we report that upregulation of COX-2 can induce overexpression of MRP4 in both A549 non-small-cell lung cancer cell lines and mouse lung cancer models...
  24. Sassi Y, Abi Gerges A, Fauconnier J, Mougenot N, Reiken S, Haghighi K, et al. Regulation of cAMP homeostasis by the efflux protein MRP4 in cardiac myocytes. FASEB J. 2012;26:1009-17 pubmed publisher
    ..This study aimed to determine whether MRP proteins regulate cardiac cAMP homeostasis. Here, we demonstrate that MRP4 is the predominant isoform present at the plasma membrane of cardiacmyocytes and that it mediates the efflux of ..
  25. Sellers Z, Naren A, Xiang Y, Best P. MRP4 and CFTR in the regulation of cAMP and ?-adrenergic contraction in cardiac myocytes. Eur J Pharmacol. 2012;681:80-7 pubmed publisher
    ..Recently, in epithelial and smooth muscle cells, it was found that the multi-drug resistant protein 4 (MRP4) acts as a cAMP efflux pump to regulate intracellular cAMP levels and alter effector function, including activation ..
  26. Hasegawa M, Kusuhara H, Adachi M, Schuetz J, Takeuchi K, Sugiyama Y. Multidrug resistance-associated protein 4 is involved in the urinary excretion of hydrochlorothiazide and furosemide. J Am Soc Nephrol. 2007;18:37-45 pubmed
    ..HCT) and furosemide was observed in membrane vesicles that expressed multidrug resistance-associated protein 4 (MRP4) and breast cancer resistance protein (BCRP)...
  27. Dankers A, Mutsaers H, Dijkman H, van den Heuvel L, Hoenderop J, Sweep F, et al. Hyperuricemia influences tryptophan metabolism via inhibition of multidrug resistance protein 4 (MRP4) and breast cancer resistance protein (BCRP). Biochim Biophys Acta. 2013;1832:1715-22 pubmed publisher
    ..and the potential role herein of two important uric acid efflux transporters, multidrug resistance protein 4 (MRP4) and breast cancer resistance protein (BCRP)...
  28. Maher J, Slitt A, Cherrington N, Cheng X, Klaassen C. Tissue distribution and hepatic and renal ontogeny of the multidrug resistance-associated protein (Mrp) family in mice. Drug Metab Dispos. 2005;33:947-55 pubmed
    ..Mrp1 in testes, ovary, and placenta; Mrp2 in intestine, followed by liver and kidney; Mrp3 in large intestine; Mrp4 in kidney; Mrp5 in brain, followed by lung and stomach; Mrp6 in liver; Mrp7 in testes, intestine, and kidney; and ..
  29. Lamba J, Adachi M, Sun D, Tammur J, Schuetz E, Allikmets R, et al. Nonsense mediated decay downregulates conserved alternatively spliced ABCC4 transcripts bearing nonsense codons. Hum Mol Genet. 2003;12:99-109 pubmed
    ..The MRPs belong to the ATP binding cassette transporter superfamily. One family member, ABCC4 (also known as MRP4) functions as a cellular efflux pump for anti-HIV drugs, such as 9-(2-phoshoenylmethoxyethyl) ..
  30. Park J, Kwak J, Riederer B, Seidler U, Cole S, Lee H, et al. Na?/H? exchanger regulatory factor 3 is critical for multidrug resistance protein 4-mediated drug efflux in the kidney. J Am Soc Nephrol. 2014;25:726-36 pubmed publisher
    ..Multidrug resistance protein 4 (MRP4) is an ATP binding cassette transporter that mediates the efflux of organic molecules, such as nucleoside analogs, ..
  31. Kruh G, Belinsky M, Gallo J, Lee K. Physiological and pharmacological functions of Mrp2, Mrp3 and Mrp4 as determined from recent studies on gene-disrupted mice. Cancer Metastasis Rev. 2007;26:5-14 pubmed
    ..Recently, mice with gene disruptions in Mrp2, Mrp3 and Mrp4 have been developed...
  32. Zelcer N, van de Wetering K, Hillebrand M, Sarton E, Kuil A, Wielinga P, et al. Mice lacking multidrug resistance protein 3 show altered morphine pharmacokinetics and morphine-6-glucuronide antinociception. Proc Natl Acad Sci U S A. 2005;102:7274-9 pubmed
    ..The pharamacokinetics of injected morphine-glucuronides are altered as well in the absence of Mrp3, and this results in a decreased antinociceptive potency of injected morphine-6-glucuronide...
  33. Matsumiya W, Kusuhara S, Hayashibe K, Maruyama K, Kusuhara H, Tagami M, et al. Forskolin modifies retinal vascular development in Mrp4-knockout mice. Invest Ophthalmol Vis Sci. 2012;53:8029-35 pubmed publisher
    Multidrug resistance protein 4 (MRP4) effluxes a wide variety of endogenous compounds, including cyclic adenosine monophosphate (cAMP), and is exclusively expressed in vascular endothelial cells (ECs) of the retina...
  34. Hayashi H, Naoi S, Nakagawa T, Nishikawa T, Fukuda H, Imajoh Ohmi S, et al. Sorting nexin 27 interacts with multidrug resistance-associated protein 4 (MRP4) and mediates internalization of MRP4. J Biol Chem. 2012;287:15054-65 pubmed publisher
    Multidrug resistance-associated protein 4 (MRP4/ABCC4) makes a vital contribution to the bodily distribution of drugs and endogenous compounds because of its cellular efflux abilities...
  35. Lin Z, Zhu Y, Johnson D, Rice K, Nottoli T, Hains B, et al. Disruption of cAMP and prostaglandin E2 transport by multidrug resistance protein 4 deficiency alters cAMP-mediated signaling and nociceptive response. Mol Pharmacol. 2008;73:243-51 pubmed
    Multidrug resistance protein 4 (MRP4; ABCC4) is a member of the MRP/ATP-binding cassette family serving as a transmembrane transporter involved in energy-dependent efflux of anticancer/antiviral nucleotide agents and of physiological ..
  36. Aleksunes L, Campion S, Goedken M, Manautou J. Acquired resistance to acetaminophen hepatotoxicity is associated with induction of multidrug resistance-associated protein 4 (Mrp4) in proliferating hepatocytes. Toxicol Sci. 2008;104:261-73 pubmed publisher
    ..Basolateral efflux transporters Mrp3 and Mrp4 are the most significantly induced...
  37. Campion S, Johnson R, Aleksunes L, Goedken M, Van Rooijen N, Scheffer G, et al. Hepatic Mrp4 induction following acetaminophen exposure is dependent on Kupffer cell function. Am J Physiol Gastrointest Liver Physiol. 2008;295:G294-304 pubmed publisher
    ..b>Mrp4 is the most significantly upregulated transporter in mouse liver following APAP treatment...
  38. Lin F, Marchetti S, Pluim D, Iusuf D, Mazzanti R, Schellens J, et al. Abcc4 together with abcb1 and abcg2 form a robust cooperative drug efflux system that restricts the brain entry of camptothecin analogues. Clin Cancer Res. 2013;19:2084-95 pubmed publisher
    Multidrug resistance-associated protein 4 (ABCC4) shares many features with P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2), including broad substrate affinity and expression at the blood-brain barrier (BBB)...
  39. Kohler J, Hosseini S, Green E, Abuin A, Ludaway T, Russ R, et al. Tenofovir renal proximal tubular toxicity is regulated by OAT1 and MRP4 transporters. Lab Invest. 2011;91:852-8 pubmed publisher
    ..In this study, the role(s) of organic anion transporter type 1 (OAT1) and multidrug-resistant protein type 4 (MRP4) in transport and regulation of tenofovir in proximal tubules were assessed...