Sodium ori'hovanadate stimulates angiothnsln iiinduced phosphoi.ipask c-γl activation in rat kidney mi-sangial cells

We have previously shown that stimulation of rat kidney glomerulai mesangial cells with the nctapeptide hormone angiolensin II (Ang II) elicits a rapid and transient ty rosi ne phosphorylation of phospholipase C-γ1 (PLC-γ1), and that this tyrosine phosphorylation is associated temporally with inositol 1.45-trisphosphate (I.4.MP₂) formation In this study, we show that incubation of mesangial cells lvith 0 1 mM sodium orthovanadate (Na₃VO₄). a protein tyrosine phosphalase inhibitor, for 30 rnin increased both the tyrosine phosphorylation of PLC-yl and the formation of 1,4,5-lP induced by Ang II fho lemporal response for the Ang II-induced tyrosine phosphorytation of Pl.r-yl and I 4.-IPi formation was similar after Na.iVCX treatment. Oollni emulation of protein kinase C (PKC) by treatment with phorbol myristate aceiate (PMA) increased the peak of Ang II-induced 1,4,5-lP. formation by 40 u The time course of 1,4,5>-IP( elevation was also extended. Downregulation of PKC also blocked the Na-A'O4 stimulation of the Ang IImdueed 1.4.>ll( formation, fhese results support our hypothesis that in mesangial cells, <lng II signal transduction functions via a PLC-yl pathway whose enzymatic activity is modulated by both tyrosine phosphorylation and PKC-mediated phosphorvlation.