Abstract
Recent studies reveal the importance of anions for regulation of cell proliferation, cell cycle, differentiation, migration and cell death. However, it is still under investigation how anions regulate cell functions. We have previously indicated in renal epithelia that: 1) the hypotonic stress causes a biphasic reduction of cytosolic Cl− concentration ([Cl−]c); a decrease in [Cl−]c during initial cell swelling followed by that during a subsequent regulatory volume decrease, and 2) the hypotonic stress modulates tyrosine phosphorylation of src kinase playing a crucial role in signal transduction. Based on these observations, we hypothesized that cytosolic Cl− acts as a signal molecule to regulate tyrosine phosphorylation in hypotonic stress in renal epithelia. To study if the cytosolic Cl− acts as a signal molecule for the hypotonic stress, we studied the effects of [Cl−]c on phosphorylation of src kinase at Tyr416. Src kinase autophosphorylates Tyr416 to show its enzymatic activation. In the absence of vanadate (a broad protein tyrosine phosphatase (PTP) inhibitor), a reduction of [Cl−]c increased phosphorylation at Tyr416. On the other hand, in the presence of vanadate, a reduction of [Cl−]c decreased phosphorylation at Tyr416. These observations suggest that: 1) both activities of PTP and src kinase decrease at lowered [Cl−]c, and 2) the activity of src kinase is larger than that PTP at lowered [Cl−]c. Supported by 17390057 and 17590191. [J Physiol Sci. 2007;57 Suppl:S61]
