{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T14:27:22Z","timestamp":1788532042592,"version":"build-2803163510"},"reference-count":58,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100019370","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/SAU-MET\/117236\/2010"],"award-info":[{"award-number":["PTDC\/SAU-MET\/117236\/2010"]}],"id":[{"id":"10.13039\/501100019370","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019370","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["UID\/MULTI\/04046\/2019"],"award-info":[{"award-number":["UID\/MULTI\/04046\/2019"]}],"id":[{"id":"10.13039\/501100019370","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019370","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD\/106080\/2015"],"award-info":[{"award-number":["SFRH\/BD\/106080\/2015"]}],"id":[{"id":"10.13039\/501100019370","id-type":"DOI","asserted-by":"publisher"}]},{"award":["PTDC\/SAU-MET\/117236\/2010"],"award-info":[{"award-number":["PTDC\/SAU-MET\/117236\/2010"]}],"id":[{"id":"https:\/\/ror.org\/00snfqn58","id-type":"ROR","asserted-by":"publisher"}]},{"award":["UID\/MULTI\/04046\/2019"],"award-info":[{"award-number":["UID\/MULTI\/04046\/2019"]}],"id":[{"id":"https:\/\/ror.org\/00snfqn58","id-type":"ROR","asserted-by":"publisher"}]},{"award":["SFRH\/BD\/106080\/2015"],"award-info":[{"award-number":["SFRH\/BD\/106080\/2015"]}],"id":[{"id":"https:\/\/ror.org\/00snfqn58","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>This manuscript is the corrected version of a previously published paper. Glucose uptake by mammalian cells is a key mechanism to maintain cell and tissue homeostasis and relies mostly on plasma membrane-localized glucose transporter proteins (GLUTs). Two main cellular mechanisms regulate GLUT proteins in the cell: first, expression of GLUT genes is under dynamic transcriptional control and is used by cancer cells to increase glucose availability. Second, GLUT proteins are regulated by membrane traffic from storage vesicles to the plasma membrane (PM). This latter process is triggered by signaling mechanisms and is well studied in the case of insulin-responsive cells, which activate protein kinase AKT to phosphorylate TBC1D4, a RAB-GTPase\u2013activating protein involved in membrane traffic regulation. Previously, we identified protein kinase WNK1 as another kinase able to phosphorylate TBC1D4 and regulate the surface abundance of the constitutive glucose transporter GLUT1. Here we describe that downregulation of WNK1 through RNA interference in HEK293 cells led to a two-fold decrease in cell-surface GLUT1 abundance, concomitant with a 40% decrease in glucose uptake. By mass spectrometry, we identified serine (S) 704 in TBC1D4 and also S565 in its paralogue TBC1D1 as candidate WNK1 phosphorylation sites. Transfection of the respective phosphomimetic or unphosphorylatable TBC1D mutants into cells revealed that both affected the cell-surface abundance of GLUT1. The results reinforce a regulatory role for WNK1 in GLUT1 trafficking and glucose uptake and may have potential impact for the understanding of metabolic dysregulation, as observed in many cancer cells or insulin-responsive cell types.<\/jats:p>","DOI":"10.3390\/cells15171582","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T01:05:26Z","timestamp":1788224726000},"page":"1582","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["WNK1 Phosphorylation Sites in TBC1D1 and TBC1D4 Modulate Cell-Surface Abundance of GLUT1"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1631-7454","authenticated-orcid":false,"given":"Andreia F. A.","family":"Henriques","sequence":"first","affiliation":[{"name":"Department of Human Genetics, National Health Institute \u2018Dr. Ricardo Jorge\u2019, 1649-016 Lisbon, Portugal"},{"name":"BioISI\u2014Instituto de Biossistemas e Ci\u00eancias Integrativas, Faculdade de Ci\u00eancias, Universidade de Lisboa, 1749-016 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9379-9696","authenticated-orcid":false,"given":"Paulo","family":"Matos","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, National Health Institute \u2018Dr. Ricardo Jorge\u2019, 1649-016 Lisbon, Portugal"},{"name":"BioISI\u2014Instituto de Biossistemas e Ci\u00eancias Integrativas, Faculdade de Ci\u00eancias, Universidade de Lisboa, 1749-016 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0657-1907","authenticated-orcid":false,"given":"Ana Sofia","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Computational and Experimental Biology Group, iNOVA4Health, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Mikel","family":"Azkargorta","sequence":"additional","affiliation":[{"name":"Proteomics Platform, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), 48160 Derio, Spain"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8839-5438","authenticated-orcid":false,"given":"Felix","family":"Elortza","sequence":"additional","affiliation":[{"name":"Proteomics Platform, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), 48160 Derio, Spain"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6353-2616","authenticated-orcid":false,"given":"Rune","family":"Matthiesen","sequence":"additional","affiliation":[{"name":"Computational and Experimental Biology Group, iNOVA4Health, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade NOVA de Lisboa, 1169-056 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1425-9211","authenticated-orcid":false,"given":"Peter","family":"Jordan","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, National Health Institute \u2018Dr. Ricardo Jorge\u2019, 1649-016 Lisbon, Portugal"},{"name":"BioISI\u2014Instituto de Biossistemas e Ci\u00eancias Integrativas, Faculdade de Ci\u00eancias, Universidade de Lisboa, 1749-016 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5562","DOI":"10.1038\/sj.onc.1204726","article-title":"WNK Kinases, a Novel Protein Kinase Subfamily in Multi-Cellular Organisms","volume":"20","author":"Jordan","year":"2001","journal-title":"Oncogene"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1096\/fasebj.9.8.7768349","article-title":"The Eukaryotic Protein Kinase Superfamily: Kinase (Catalytic) Domain Structure and Classification","volume":"9","author":"Hanks","year":"1995","journal-title":"FASEB J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1126\/science.1075762","article-title":"The Protein Kinase Complement of the Human Genome","volume":"298","author":"Manning","year":"2002","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"16795","DOI":"10.1074\/jbc.275.22.16795","article-title":"WNK1, a Novel Mammalian Serine\/Threonine Protein Kinase Lacking the Catalytic Lysine in Subdomain II","volume":"275","author":"Xu","year":"2000","journal-title":"J. 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