{"citation":{"short":"B. Krueger, L. Yang, C. Korbmacher, R. Rauh, Pflügers Archiv - European Journal of Physiology 470 (2018) 649–660.","ama":"Krueger B, Yang L, Korbmacher C, Rauh R. The phosphorylation site T613 in the $\\beta$-subunit of rat epithelial Na+ channel (ENaC) modulates channel inhibition by Nedd4-2. <i>Pflügers Archiv - European Journal of Physiology</i>. 2018;470(4):649–660. doi:<a href=\"https://doi.org/10.1007/s00424-018-2115-2\">10.1007/s00424-018-2115-2</a>","bibtex":"@article{Krueger_Yang_Korbmacher_Rauh_2018, title={The phosphorylation site T613 in the $\\beta$-subunit of rat epithelial Na+ channel (ENaC) modulates channel inhibition by Nedd4-2}, volume={470}, DOI={<a href=\"https://doi.org/10.1007/s00424-018-2115-2\">10.1007/s00424-018-2115-2</a>}, number={4}, journal={Pflügers Archiv - European Journal of Physiology}, publisher={Springer}, author={Krueger, Bettina and Yang, Limin and Korbmacher, Christoph and Rauh, Robert}, year={2018}, pages={649–660} }","mla":"Krueger, Bettina, et al. “The Phosphorylation Site T613 in the $\\beta$-Subunit of Rat Epithelial Na+ Channel (ENaC) Modulates Channel Inhibition by Nedd4-2.” <i>Pflügers Archiv - European Journal of Physiology</i>, vol. 470, no. 4, Springer, 2018, pp. 649–660, doi:<a href=\"https://doi.org/10.1007/s00424-018-2115-2\">10.1007/s00424-018-2115-2</a>.","ieee":"B. Krueger, L. Yang, C. Korbmacher, and R. Rauh, “The phosphorylation site T613 in the $\\beta$-subunit of rat epithelial Na+ channel (ENaC) modulates channel inhibition by Nedd4-2,” <i>Pflügers Archiv - European Journal of Physiology</i>, vol. 470, no. 4, pp. 649–660, 2018, doi: <a href=\"https://doi.org/10.1007/s00424-018-2115-2\">10.1007/s00424-018-2115-2</a>.","chicago":"Krueger, Bettina, Limin Yang, Christoph Korbmacher, and Robert Rauh. “The Phosphorylation Site T613 in the $\\beta$-Subunit of Rat Epithelial Na+ Channel (ENaC) Modulates Channel Inhibition by Nedd4-2.” <i>Pflügers Archiv - European Journal of Physiology</i> 470, no. 4 (2018): 649–660. <a href=\"https://doi.org/10.1007/s00424-018-2115-2\">https://doi.org/10.1007/s00424-018-2115-2</a>.","apa":"Krueger, B., Yang, L., Korbmacher, C., &#38; Rauh, R. (2018). The phosphorylation site T613 in the $\\beta$-subunit of rat epithelial Na+ channel (ENaC) modulates channel inhibition by Nedd4-2. <i>Pflügers Archiv - European Journal of Physiology</i>, <i>470</i>(4), 649–660. <a href=\"https://doi.org/10.1007/s00424-018-2115-2\">https://doi.org/10.1007/s00424-018-2115-2</a>"},"_id":"54928","page":"649–660","publication":"Pflügers Archiv - European Journal of Physiology","abstract":[{"text":"The epithelial Na+ channel (ENaC) is a heteromeric channel composed of three subunits ($\\alpha$, $\\beta$, $\\gamma$). At the C-terminus of each subunit, a PY-motif allows binding of the ubiquitin ligase Nedd4-2 which plays a key role in promoting ENaC retrieval from the plasma membrane. Phosphorylation of Nedd4-2 by the serum and glucocorticoid-inducible kinase 1 (Sgk1) reduces Nedd4-2 binding to the PY-motifs. In $\\beta$ and $\\gamma$ENaC, threonine residues ($\\beta$T613, $\\gamma$T623) belong to an extracellular signal-regulated kinase (ERK) motif and directly precede the PY-motifs. Thus, phosphorylation of these residues may modulate the interaction of their adjacent PY-motifs with Nedd4-2. In this study, a phosphospecific antibody was used to demonstrate phosphorylation of $\\beta$T613 in Xenopus laevis oocytes heterologously expressing rat $\\alpha$$\\beta$$\\gamma$ENaC. Treating the oocytes with progesterone to stimulate ERK increased phosphorylation of $\\beta$T613. Inactivation of the putative phosphorylation sites by mutating both threonine residues to alanine ($\\beta$T613A/$\\gamma$T623A) increased ENaC-mediated amiloride-sensitive whole-cell currents ($\\Delta$Iami) and expression of $\\beta$ENaC at the cell surface. Co-expression of Nedd4-2 largely reduced $\\Delta$Iami in oocytes expressing $\\alpha$$\\beta$$\\gamma$ENaC or channels with mutated PY-motifs in $\\alpha$ and $\\gamma$ENaC or in $\\alpha$ and $\\beta$ENaC. Importantly, the inhibitory effect of co-expressed Nedd4-2 was largely reduced in channels with mutated PY-motifs in $\\alpha$ and $\\gamma$ENaC when combined with the $\\beta$T613A mutation but conserved in channels with mutated PY-motifs in $\\alpha$ and $\\beta$ENaC combined with the $\\gamma$T623A mutation. These results suggest that phosphorylation and dephosphorylation of $\\beta$T613 play a prominent role in regulating Nedd4-2-mediated ENaC retrieval from the plasma membrane.","lang":"eng"}],"intvolume":"       470","date_created":"2024-06-30T13:43:17Z","doi":"10.1007/s00424-018-2115-2","date_updated":"2024-06-30T13:43:39Z","status":"public","volume":470,"issue":"4","year":"2018","title":"The phosphorylation site T613 in the $\\beta$-subunit of rat epithelial Na+ channel (ENaC) modulates channel inhibition by Nedd4-2","language":[{"iso":"eng"}],"publisher":"Springer","department":[{"_id":"35"},{"_id":"22"}],"type":"journal_article","user_id":"49428","author":[{"full_name":"Krueger, Bettina","last_name":"Krueger","id":"49428","orcid":"0000-0001-5351-1785","first_name":"Bettina"},{"last_name":"Yang","full_name":"Yang, Limin","first_name":"Limin"},{"last_name":"Korbmacher","full_name":"Korbmacher, Christoph","first_name":"Christoph"},{"last_name":"Rauh","full_name":"Rauh, Robert","first_name":"Robert"}]}