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Hypotonicity stimulates Na+ reabsorption through activation of src kinase by decreasing cytosolic Cl‐ concentration
Author(s) -
Niisato Naomi,
Marunaka Yoshinori
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.a346-d
Subject(s) - proto oncogene tyrosine protein kinase src , tyrosine kinase , reabsorption , epithelial sodium channel , chemistry , phosphorylation , medicine , endocrinology , cytosol , renal sodium reabsorption , kinase , tyrosine phosphorylation , signal transduction , biology , sodium , biochemistry , enzyme , kidney , organic chemistry
We have previously indicated that in renal epithelial A6 cells hypotonicity stimulates Na+ reabsorption by activating a PTK‐dependent pathway and that hypotonicity causes a decrease in cytosolic Cl‐ concentration ([Cl−]c) through regulatory volume decrease (RVD). In this study, we found that hypotonicity increased tyrosine phosphorylation of src kinase at pY416 (an active form of src kinase) in a manner dependent on RVD‐induced [Cl−]c decrease. We further found that decreasing [Cl−]c caused a significant increase in tyrosine phosphorylation of src kinase at pY416 under an isotonic condition without any effect on tyrosine phosphorylation state of src kinase at pY527. Furthermore, pretreatment with PP2 (a specific inhibitor of src kinase) abolished hypotonicity‐induced stimulation of Na+ rebasorption and alpha‐subunit of epithelial Na+ channel (ENaC) mRNA expression. Taken together these results, it is suggested that hypotonicity stimuates Na+ rebasorption through induction of alpha‐ENaC gene expression by activating src kinase through RVD‐dependent decrease in [Cl−]c. Supported by Grants‐in‐Aids from JSPS (17590191 and 17390057).