ArticleThe Journal of biological chemistry2013
Multi-drug resistance protein 4 (MRP4)-mediated regulation of fibroblast cell migration reflects a dichotomous role of intracellular cyclic nucleotides.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- Protein Kinase A and assembly of an ABCC4 protein network.Nature communications · 2025Article
- The multidrug resistance protein inhibitor, MK571 inhibits the hypercontractility state in prostate from obese mice.World journal of urology · 2025Article
- Differential Selectivity of Human and Mouse ABCC4/Abcc4 for Arsenic Metabolites.Drug metabolism and disposition: the biological fate of chemicals · 2024Article
- Article
- Cyclic AMP efflux through MRP4 regulates actin dynamics signalling pathway and sperm motility in bovines.Scientific reports · 2020Article
- Multidrug transporter MRP4/ABCC4 as a key determinant of pancreatic cancer aggressiveness.Scientific reports · 2020Article
- Functional Expression of Multidrug Resistance Protein 4 MRP4/ABCC4.SLAS discovery : advancing life sciences R & D · 2019Article
- Article
- Cell Migration Related to MDR-Another Impediment to Effective Chemotherapy?Molecules (Basel, Switzerland) · 2018Review
- Eupatolide inhibits the TGF-β1-induced migration of breast cancer cells via downregulation of SMAD3 phosphorylation and transcriptional repression of ALK5.Oncology letters · 2017Article
- Multiple drug resistance-associated protein (MRP4) exports prostaglandin E2 (PGE2) and contributes to metastasis in basal/triple negative breast cancer.Oncotarget · 2017Article
- Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration.Journal of visualized experiments : JoVE · 2016Article
- Article
- Drug Transporters and Na+/H+ Exchange Regulatory Factor PSD-95/Drosophila Discs Large/ZO-1 Proteins.Pharmacological reviews · 2015Review
- PKA and actin play critical roles as downstream effectors in MRP4-mediated regulation of fibroblast migration.Cellular signalling · 2015Article
- Blockade of Multidrug Resistance-Associated Proteins Aggravates Acute Pancreatitis and Blunts Atrial Natriuretic Factor's Beneficial Effect in Rats: Role of MRP4 (ABCC4).Molecular medicine (Cambridge, Mass.) · 2015Article
- Leukemia and ABC transporters.Advances in cancer research · 2015Review
- Asymmetrical macromolecular complex formation of lysophosphatidic acid receptor 2 (LPA2) mediates gradient sensing in fibroblasts.The Journal of biological chemistry · 2014Article
- Förster resonance energy transfer - an approach to visualize the spatiotemporal regulation of macromolecular complex formation and compartmentalized cell signaling.Biochimica et biophysica acta · 2014Review
- Compartmentalization of cyclic nucleotide signaling: a question of when, where, and why?Pflugers Archiv : European journal of physiology · 2013Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
It has long been known that cyclic nucleotides and cyclic nucleotide-dependent signaling molecules control cell migration. However, the concept that it is not just the absence or presence of cyclic nucleotides, but a highly coordinated balance between these molecules that regulates cell migration, is new and revolutionary. 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 to explore this unique and emerging concept. MRP4, a member of a large family of ATP binding cassette transporter proteins, localizes to the plasma membrane and functions as a nucleotide efflux transporter and thus plays a role in the regulation of intracellular cyclic nucleotide levels. Here, we demonstrate that mouse embryonic fibroblasts (MEFs) isolated from Mrp4(-/-) mice have higher intracellular cyclic nucleotide levels and migrate faster compared with MEFs from Mrp4(+/+) mice. Using FRET-based cAMP and cGMP sensors, we show that inhibition of MRP4 with MK571 increases both cAMP and cGMP levels, which results in increased migration. In contrast to these moderate increases in cAMP and cGMP levels seen in the absence of MRP4, a robust increase in cAMP levels was observed following treatment with forskolin and isobutylmethylxanthine, which decreases fibroblast migration. In response to externally added cell-permeant cyclic nucleotides (cpt-cAMP and cpt-cGMP), MEF migration appears to be biphasic. Altogether, our studies provide the first experimental evidence supporting the novel concept that balance between cyclic nucleotides is critical for cell migration.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.