Research ArticleION TRANSPORT

Modulation of Cl signaling and ion transport by recruitment of kinases and phosphatases mediated by the regulatory protein IRBIT

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Science Signaling  30 Oct 2018:
Vol. 11, Issue 554, eaat5018
DOI: 10.1126/scisignal.aat5018

Combinations to regulate Cl signaling

The secretion of HCO3-containing fluids is vital to the function of all epithelia and is enabled in part by the activity of the Na+-coupled HCO3 transporter NBCe1-B. Vachel et al. identified five serine residues in NBCe1-B whose phosphorylation status was controlled by the regulatory protein IRBIT. The phosphorylation status of Ser12 and Ser65 affected the Cl sensitivity of two intracellular Cl-sensing motifs. Moreover, IRBIT recruited a distinct kinase/phosphatase pair for each serine residue. The three remaining phosphorylation sites were phosphorylated in distinct combinations that determined the relative basal activity level of NBCe1-B and the potential for further activation by IRBIT. These results demonstrate how distinct phosphorylation patterns may enable epithelial cells to fine-tune the HCO3 transport activity of NBCe1-B in response to varying conditions in different parts of the organ.

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