Regulation of the renal Na-HCO3 cotransporter. XI. Signal transduction underlying CO2stimulation.
Regulation of the renal Na-HCO3 cotransporter. XI. Signal transduction underlying CO2stimulation.
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DOI：
10.1152/ajprenal.1999.277.4.f580
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发表时间：
1999-10
期刊：
影响因子：
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通讯作者：
O. Ruiz;R. Robey;Y. Qiu;L. Wang;Cheng Jin Li;Jianfei Ma;J. Arruda
中科院分区：
文献类型：
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作者：
O. Ruiz;R. Robey;Y. Qiu;L. Wang;Cheng Jin Li;Jianfei Ma;J. Arruda
我们以前已经表明，CO2刺激肾Na-HCO 3协同转运蛋白（NBC）的活动被废除的一般抑制剂的蛋白酪氨酸激酶。选择性更强的抑制剂除莠霉素也在已知优先抑制Src家族激酶（SFK）的浓度下阻断了这种效应。因此，我们研究了SFKs在CO2刺激的NBC活动中的作用。为此，我们设计了OK细胞来表达COOH末端Src激酶（Csk），这是SFKs的负调节因子。在表达β-半乳糖苷酶的细胞和未转染的对照细胞中，CO2正常刺激NBC活性。相反，表达Csk的细胞具有正常的基线NBC活性，不受CO2刺激。CO2刺激增加总SFK活性和Src的特异性酪氨酸磷酸化。特异性MEK 1/2抑制剂PD-98059完全抑制CO2刺激的NBC活性以及伴随的ERK 1/2磷酸化和活化。我们的数据表明，参与SFKs，可能Src，和“经典”MAPK途径介导的CO2刺激的NBC活性在肾上皮细胞。
We have previously shown that CO2 stimulation of the renal Na-HCO3 cotransporter (NBC) activity is abrogated by general inhibitors of protein tyrosine kinases. The more selective inhibitor herbimycin also blocked this effect at concentrations known to preferentially inhibit Src family kinases (SFKs). We therefore examined a role for SFKs in CO2-stimulated NBC activity. To this end, we engineered OK cells to express the COOH-terminal Src kinase (Csk), a negative regulator of SFKs. CO2 stimulated NBC activity normally in β-galactosidase-expressing and untransfected control cells. In contrast, Csk-expressing cells had normal baseline NBC activity that was not stimulated by CO2. CO2 stimulation increased both total SFK activity and specific tyrosine phosphorylation of Src. The specific MEK1/2 inhibitor PD-98059 completely inhibited the CO2 stimulation of NBC activity as well as the accompanying phosphorylation and activation of ERK1/2. Our data suggest the involvement of both SFKs, probably Src, and the "classic" MAPK pathway in mediating CO2-stimulated NBC activity in renal epithelial cells.