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Epidermal Growth Factor Activates Na+/H+ Exchange in Podocytes through a Mechanism that Involves Janus Kinase and Calmodulin
Author(s) -
Coaxum Sonya D,
Gooz Monika,
Baldys Aleksander,
Garnovskaya Maria N,
Raymond John R
Publication year - 2006
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.20.4.a764
Subject(s) - mechanism (biology) , microbiology and biotechnology , calmodulin , janus kinase , chemistry , kinase , epidermal growth factor , biology , biochemistry , physics , enzyme , receptor , quantum mechanics
Previous studies from our laboratory have shown that the NHE‐1 can be activated by G protein‐coupled receptors or hypertonic medium, through janus kinase 2 (Jak2)‐dependent phosphorylation of calmodulin (CaM) and subsequent interaction between CaM and NHE‐1. Therefore, we wanted to determine whether the EGF receptor regulated NHE‐1 activity through Jak2 and CaM. EGF induced concentration‐dependent increases in proton efflux in renal podocytes as accessed using a Cytosensor microphysiometer. Stimulation of proton efflux by EGF in podocytes was diminished in the presence of MIA or a sodium‐free solution, which demonstrates that EGF stimulates a sodium‐dependent proton efflux that can be attenuated by a selective NHE‐1 inhibitor in podocytes. Furthermore, inhibitors of Jak2 and calmodulin attenuated EGF‐induced NHE‐1 activity. Co‐immunoprecipitation studies determined that EGF induced formation of complexes between Jak2, CaM, and NHE‐1. We found that there were increased amounts of NHE‐1 and calmodulin assembled with Jak2 upon EGF stimulation. The results suggest that EGF induces NHE‐1 activity in podocytes through Jak2 and increased interaction between CaM and NHE‐1. This work was supported by Veterans Affairs Merit Award and NIH R01DK052448.