{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T21:21:17Z","timestamp":1778275277697,"version":"3.51.4"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2003,6,1]],"date-time":"2003-06-01T00:00:00Z","timestamp":1054425600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2003,6]]},"abstract":"<jats:p>The human <jats:italic>NBC1<\/jats:italic> (<jats:italic>SLC4A4<\/jats:italic>) gene encodes the electrogenic sodium bicarbonate cotransporters kNBC1 and pNBC1, which are highly expressed in the kidney and pancreas, respectively. The HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>:Na<jats:sup>+<\/jats:sup> stoichiometry of these cotransporters is an important determinant of the direction of ion flux. Recently we showed in a mouse proximal tubule (mPCT) cell line expressing kNBC1, that 8\u2010Br\u2010cAMP shifts the stoichiometry of the cotransporter from 3:1 to 2:1 via protein kinase A (PKA)\u2010dependent phosphorylation of Ser<jats:sup>982<\/jats:sup>. pNBC1 has the identical carboxy\u2010terminal consensus phosphorylation PKA site (KKGS<jats:sup>1026<\/jats:sup>), and an additional site in its amino\u2010terminus (KRKT<jats:sup>49<\/jats:sup>). In this study we determined the potential role of these sites in regulating the function of pNBC1. The results demonstrated that in mPCT cells expressing pNBC1, PKA\u2010dependent phosphorylation of Ser<jats:sup>1026<\/jats:sup> following 8\u2010Br\u2010cAMP treatment shifted the stoichiometry from 3:1 to 2:1. The effect was electrostatic in nature as replacing Ser<jats:sup>1026<\/jats:sup> with Asp resulted in a similar stoichiometry shift. In addition to shifting the stoichiometry, 8\u2010Br\u2010cAMP caused a significant increase in the 4,4\u2032\u2010dinitrostilbene\u20102,2\u2032\u2010disulfonic acid (DNDS)\u2010sensitive basolateral membrane conductance (<jats:italic>G<\/jats:italic><jats:sub>DS<\/jats:sub>) of cells expressing pNBC1, but not kNBC1. Although, the effect did not involve phosphorylation of Thr<jats:sup>49<\/jats:sup>, which was endogenously phosphorylated, replacing this residue with Asp or Ala abolished the 8\u2010Br\u2010cAMP\u2010induced increase in <jats:italic>G<\/jats:italic><jats:sub>DS<\/jats:sub>. In the mPEC pancreatic duct cell line, where endogenous pNBC1 functions with a HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>:Na<jats:sup>+<\/jats:sup> stoichiometry of 2:1, 8\u2010Br\u2010cAMP increased <jats:italic>G<\/jats:italic><jats:sub>DS<\/jats:sub> by \u223c90 % without altering the stoichiometry or inducing phosphorylation of the cotransporter. The results demonstrate that phosphorylation of Ser<jats:sup>1026<\/jats:sup> mediates the cAMP\u2010dependent shift in the stoichiometry of pNBC1, whereas Thr<jats:sup>49<\/jats:sup> plays an essential role in the cAMP\u2010induced increase in <jats:italic>G<\/jats:italic><jats:sub>DS<\/jats:sub>.<\/jats:p>","DOI":"10.1113\/jphysiol.2003.042226","type":"journal-article","created":{"date-parts":[[2003,5,6]],"date-time":"2003-05-06T00:16:14Z","timestamp":1052180174000},"page":"673-682","source":"Crossref","is-referenced-by-count":45,"title":["Phosphorylation\u2010Induced Modulation of pNBC1 Function: Distinct Roles for the Amino\u2010 and Carboxy\u2010Termini"],"prefix":"10.1113","volume":"549","author":[{"given":"E.","family":"Gross","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"O.","family":"Fedotoff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Pushkin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Abuladze","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Newman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I.","family":"Kurtz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2003,6]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.28.17689"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(00)00204-3"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2001.281.5.F920"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.31.19111"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M000600200"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2001.0375i.x"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2001.0597h.x"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2001.00659.x"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00148.2002"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.029777"},{"key":"e_1_2_5_12_1","first-page":"61A","article-title":"Phosphorylation 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