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Opposite effects of WNK3 and WNK4 upon the Slc26a9 anion transporter/channel.
Author(s) -
Plata Consuelo,
Vázquez Norma,
F Romero Michael,
Gamba Gerardo
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1202.9
Subject(s) - chemistry , kinase , cotransporter , ion transporter , xenopus , biochemistry , sodium , gene , membrane , organic chemistry
Slc26a9 is an electrogenic n Cl − /HCO 3 − exchanger with a large anion conductance that is mainly expressed in respiratory and gastrointestinal epithelial cells. It was recently shown that Slc26a9 is negatively regulated by the serine/threonine kinases WNK1, WNK3, and WNK4, and that these effects were not dependent upon the kinase activity. However, WNK3 and WNK4 have been shown to exhibit opposite effects in other chloride cotransporters. To gain insight to putative kinase regulation of Slc26a9, we evaluated the effect of protein kinases WNK3 and WNK4 on Slc26a9‐mediated anion transport using 36 Cl − uptake in Xenopus laevis oocytes. Oocytes were injected with Slc26a9‐cRNA alone or together with WNK4 or WNK3‐cRNA. We observed that WNK4 caused a ~30% decrease in 36 Cl − uptake by Slc26a9. This inhibition was not observed with co‐injection of D318A‐WNK4 which renders WNK4 catalytically inactive. Co‐injection of oocytes with Slc26a9 and WNK3 increased Slc26a9 activity by ~40% above baseline. This increased Slc26a9 activity by WNK3 was also kinase dependent, i.e., Slc26a9 activation was eliminated by D294A‐WNK3 which renders WNK3 catalytically inactive. Thus, our data indicate that WNK3 is a positive regulator of transport Cl − and WNK4 is a negative regulator of Cl − transport by the Slc26a9 anion transporter/channel. Furthermore, this Slc26a9 transport regulation is dependent on kinase activity of WNK3 and WNK4.