Dominant negative c-Src inhibits angiotensin II induced activation of NHE3 in OKP cells.

Dominant negative c-Src inhibits angiotensin II induced activation of NHE3 in OKP cells.
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显性负性 c-Src 抑制 OKP 细胞中血管紧张素 II 诱导的 NHE3 激活。

DOI:
10.1046/j.1523-1755.1998.00029.x
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发表时间:
1998
影响因子:
19.6
通讯作者:
Alpern,RJ
Alpern,RJ
中科院分区:
医学1区
文献类型:
--
作者:
Tsuganezawa,H;Preisig,PA;Alpern,RJ

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Dominant negative c-Src inhibits angiotensin II induced activation of NHE3 in OKP cells.BackgroundAngiotensin II is a potent stimulator of the proximal tubule apical membrane Na/H antiporter, encoded by NHE3. The nonreceptor tyrosine kinase, c-Src, plays a key role in regulation of NHE3 by acidosis in the proximal tubule, and in signaling effects of angiotensin II in vascular smooth muscle.MethodsThe present studies examined the role of c-Src in mediating angiotensin II-induced NHE3 activation in cultured OKP cells. c-Src was inhibited with herbimycin A, a tyrosine kinase inhibitor, and expression of a dominant negative c-Src, c-SrcK295M.ResultsHerbimycin A blocked angiotensin II induced increases in Na/H antiporter activity. In two clonal cell lines expressing vector alone, angiotensin II increased Na/H antiporter activity, while in three clones expressing c-SrcK295M, angiotensin II had no effect. Cyclic AMP and protein kinase A have been proposed to be key mediators in regulation of NHE3 by angiotensin II. 10-4m8-bromo cAMP induced a 40 to 50% inhibition of Na/H antiporter activity in cells expressing c-SrcK295M, similar to that seen in wild-type OKP cells. In addition, cells expressing c-SrcK295Mresponded normally to 10-7mdexamethasone with a 50 to 80% increase in Na/H antiporter activity.ConclusionsThese studies demonstrate that c-Src is required for angiotensin II-induced increases in NHE3 activity. Thus, c-Src plays a key role in antiporter activation by acidosis and angiotensin II.
DOI: 10.1073/pnas.87.20.7917
发表时间: 1990-10-01
影响因子: 11.1
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GEIBEL, J;GIEBISCH, G;BORON, WF
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DOI: --
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期刊: Kidney international. Supplement
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