ArticleThe Journal of biological chemistry2008
Negative regulation of the yeast ABC transporter Ycf1p by phosphorylation within its N-terminal extension.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 55 citations in OpenAlex.
- Structure of a dimeric full-length ABC transporter.Nature communications · 2024Article
- Multilevel Regulation of Membrane Proteins in Response to Metal and Metalloid Stress: A Lesson from Yeast.International journal of molecular sciences · 2024Review
- Article
- B cell linker protein (BLNK) is a regulator of Met receptor signaling and trafficking in non-small cell lung cancer.iScience · 2022Article
- The structural basis for regulation of the glutathione transporter Ycf1 by regulatory domain phosphorylation.Nature communications · 2022Article
- CFTR interactome mapping using the mammalian membrane two-hybrid high-throughput screening system.Molecular systems biology · 2022Article
- Structure of Ycf1p reveals the transmembrane domain TMD0 and the regulatory region of ABCC transporters.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Highly Combinatorial Genetic Interaction Analysis Reveals a Multi-Drug Transporter Influence Network.Cell systems · 2020Article
- Quantitative phosphoproteomic analyses provide evidence for extensive phosphorylation of regulatory proteins in the rhizobia-legume symbiosis.Plant molecular biology · 2019Article
- Identification and Functional Testing of Novel Interacting Protein Partners for the Stress Sensors Wsc1p and Mid2p ofG3 (Bethesda, Md.) · 2019Article
- Vacuolar Sequestration of Azoles, a Novel Strategy of Azole Antifungal Resistance Conserved across Pathogenic and Nonpathogenic Yeast.Antimicrobial agents and chemotherapy · 2019Article
- Beyond Competitive Inhibition: Regulation of ABC Transporters by Kinases and Protein-Protein Interactions as Potential Mechanisms of Drug-Drug Interactions.Drug metabolism and disposition: the biological fate of chemicals · 2018Review
- Positive regulation of the Candida albicans multidrug efflux pump Cdr1p function by phosphorylation of its N-terminal extension.The Journal of antimicrobial chemotherapy · 2016Article
- Development of a membrane-anchored ligand and receptor yeast two-hybrid system for ligand-receptor interaction identification.Scientific reports · 2016Article
- New insights into the roles of the N-terminal region of the ABCC6 transporter.Journal of bioenergetics and biomembranes · 2016Article
- Bimolecular Fluorescence Complementation (BiFC) Analysis: Advances and Recent Applications for Genome-Wide Interaction Studies.Journal of molecular biology · 2015Review
- A Comprehensive Membrane Interactome Mapping of Sho1p Reveals Fps1p as a Novel Key Player in the Regulation of the HOG Pathway in S. cerevisiae.Journal of molecular biology · 2015Article
- YCF1-mediated cadmium resistance in yeast is dependent on copper metabolism and antioxidant enzymes.Antioxidants & redox signaling · 2014Article
- Identification of genes expressed by Cryptococcus gattii during iron deprivation.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2014Article
- Quantitative phosphoproteomic analysis of soybean root hairs inoculated with Bradyrhizobium japonicum.Molecular & cellular proteomics : MCP · 2012Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The yeast vacuolar membrane protein Ycf1p and its mammalian counterpart, MRP1, belong to the ABCC subfamily of ATP-binding cassette (ABC) transporters that rid cells of toxic endogenous and xenobiotic compounds. Like most members of the ABCC subfamily, Ycf1p contains an N-terminal extension in addition to its ABC "core" domain and transports substrates in the form of glutathione conjugates. Ycf1p is subject to complex regulation to ensure its optimal function. Previous studies showed that Ycf1p activity is stimulated by a guanine nucleotide exchange factor, Tus1p, and is positively regulated by phosphorylation in its ABC core domain at residues Ser-908 and Thr-911. Here we provide evidence that phosphorylation of Ser-251 in the Ycf1p N-terminal extension negatively regulates activity. Mutant Ycf1p-S251A exhibits increased resistance to cadmium in vivo and increased Ycf1p-dependent transport of [(3)H]estradiol-beta-17-glucuronide in vitro as compared with wild-type Ycf1p. Activity is restored to the wild-type level for Ycf1-S251E. To identify kinase(s) that negatively regulate Ycf1p function, we conducted an integrated membrane yeast two-hybrid (iMYTH) screen and identified two kinase genes, CKA1 and HAL5, deletion of which increases Ycf1p function. Genetic evidence suggests that Cka1p may regulate Ycf1p function through phosphorylation of Ser-251 either directly or indirectly. Overall, this study provides compelling evidence that negative, as well as positive, regulation of Ycf1p is mediated by phosphorylation.
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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.