ABCMdb

PMID: 11053017

Baldursson O, Berger HA, Welsh MJ
Contribution of R domain phosphoserines to the function of CFTR studied in Fischer rat thyroid epithelia.
Am J Physiol Lung Cell Mol Physiol. 2000 Nov;279(5):L835-41., [PubMed]

Sentences

No. Mutations Sentence Comment

14 ABCC7 p.Ser737Ala Changing Ser737 to alanine increased current above wild-type levels, suggesting that phosphorylation of Ser737 may inhibit current in wild-type CFTR. Login to comment 56 ABCC7 p.Ser660Ala ABCC7 p.Ser737Ala ABCC7 p.Ser795Ala ABCC7 p.Ser813Ala In each of the serine to alanine mutants, S660A, S737A, S795A, and S813A, alanine replaced serine at the designated residue. Login to comment 107 ABCC7 p.Ser660Ala ABCC7 p.Ser813Ala The S660A and S813A variants generated small but significant cAMP-stimulated Cl- currents. Login to comment 108 ABCC7 p.Ser737Ala ABCC7 p.Ser795Ala The S795A channels generated more current, but it was still less than that produced by wild-type CFTR. Interestingly, current from the S737A variant tended to be greater than that of wild-type CFTR, although the difference was not significant. Login to comment 112 ABCC7 p.Ser660Ala ABCC7 p.Ser813Ala The S660A and S813A variants generated currents, but they were no greater than those obtained with SQuad-A. Login to comment 114 ABCC7 p.Ser737Ala ABCC7 p.Ser795Ala Current from the S795A variant was not different from that in wild-type CFTR. Interestingly, current generated by the S737A variant was more than twice that generated by wild-type CFTR. Login to comment 134 ABCC7 p.Ser737Ala The S737A variant generated more current than the wild type, and the S-Quad-A mutant generated less. Login to comment 137 ABCC7 p.Ser737Ala The data show that the S-Quad-A variant was less sensitive to forskolin than the wild type and that the S737A variant was more sensitive than wild-type CFTR. Login to comment 140 ABCC7 p.Ser737Ala The results show that current increased more rapidly with S737A than with wild-type and S-Quad-A CFTR. Login to comment 152 ABCC7 p.Ser737Ala The increase in current and the more rapid activation observed when Ser737 was mutated to alanine suggested that phosphorylation of Ser737 may inhibit current. Login to comment 157 ABCC7 p.Ser737Ala Activation by increasing concentrations of forskolin of Cl- current in epithelia expressing wild-type CFTR, S737A, and SQuad-A. Login to comment 161 ABCC7 p.Ser737Ala C: current in epithelia expressing wild-type CFTR, S737A, and S-Quad-A in response to forskolin. Login to comment 186 ABCC7 p.Ser660Ala ABCC7 p.Ser813Ala Mutation of either residue alone significantly decreased current; with maximal stimulation by cAMP agonists, neither the S660A nor the S813A mutant gave more current than the S-Quad-A Fig. 5. Login to comment 187 ABCC7 p.Ser737Ala Time course of Cl- current activation in epithelia expressing wild-type CFTR, S737A, and S-Quad-A. Login to comment 195 ABCC7 p.Ser660Ala ABCC7 p.Ser813Ala With submaximal cAMP agonists, S660A- and S813A-generated current was also reduced, but it was slightly greater than that obtained with S-Quad-A. Login to comment 205 ABCC7 p.Ser795Ala This result is different from studies in excised patches of membrane showing that S795A reduced open state probability (29). Login to comment 225 ABCC7 p.Ser737Ala A particularly striking example is the different function of S737A in cells and in excised membrane patches. Login to comment 226 ABCC7 p.Ser737Ala In FRT cells and in Xenopus oocytes (28), Ser737 generated more current than wild-type CFTR, but, in patches, S737A showed the same open state probability as the wild type, and the sensitivity to ATP was reduced (29). Login to comment