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首页> 外文期刊>American Journal of Physiology >A consensus sequence in the endothelin-B receptor second intracellular loop is required for NHE3 activation by endothelin-1.
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A consensus sequence in the endothelin-B receptor second intracellular loop is required for NHE3 activation by endothelin-1.

机译：内皮素B激活NHE3需要内皮素B受体第二个细胞内环中的共有序列。

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摘要

Endothelin-1 (ET-1) increases the activity of Na(+)/H(+) exchanger 3 (NHE3), the major proximal tubule apical membrane Na(+)/H(+) antiporter. This effect is seen in opossum kidney (OKP) cells expressing the endothelin-B (ET(B)) and not in cells expressing the endothelin-A (ET(A)) receptor. However, ET-1 causes similar patterns of protein tyrosine phosphorylation, adenylyl cyclase inhibition, and increases in cell [Ca(2+)] in ET(A)- and ET(B)-expressing OKP cells, implying that an additional mechanism is required for NHE3 stimulation by the ET(B) receptor. The present studies used ET(A) and ET(B) receptor chimeras and site-directed mutagenesis to identify the ET receptor domains that mediate ET-1 regulation of NHE3 activity. We found that binding of ET-1 to the ET(A) receptor inhibits NHE3 activity, an effect for which the COOH-terminal tail is necessary and sufficient. ET-1 stimulation of NHE3 activity requires the COOH-terminal tail and the second intracellular loop of the ET(B) receptor. Within the second intracellular loop, a consensus sequence was identified, KXXXVPKXXXV, that is required for ET-1 stimulation of NHE3 activity. This sequence suggests binding of a homodimeric protein that mediates NHE3 stimulation.
机译：内皮素-1（ET-1）增加Na（+）/ H（+）交换子3（NHE3），主要近端小管顶膜Na（+）/ H（+）反向转运蛋白的活性。在表达内皮素B（ET（B））的负鼠肾（OKP）细胞中而不是在表达内皮素A（ET（A））受体的细胞中看到这种效果。但是，ET-1引起蛋白质酪氨酸磷酸化，腺苷酸环化酶抑制的相似模式，并在表达ET（A）和ET（B）的OKP细胞中的细胞[Ca（2+）]中增加，这表明存在其他机制ET（B）受体刺激NHE3所需。本研究使用ET（A）和ET（B）受体嵌合体和定点诱变来鉴定介导ET-1调节NHE3活性的ET受体域。我们发现，ET-1与ET（A）受体的结合会抑制NHE3活性，而COOH末端尾部是必需且充分的。 ET-1刺激NHE3活性需要COOH末端尾巴和ET（B）受体的第二个细胞内环。在第二个细胞内环中，确定了一个共有序列，即KXXXVPKXXXV，它是ET-1刺激NHE3活性所必需的。该序列表明介导NHE3刺激的同型二聚体蛋白的结合。

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