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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >CAMP-MEDIATED INHIBITION OF THE EPITHELIAL BRUSH BORDER NA+/H+ EXCHANGER, NHE3, REQUIRES AN ASSOCIATED REGULATORY PROTEIN
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CAMP-MEDIATED INHIBITION OF THE EPITHELIAL BRUSH BORDER NA+/H+ EXCHANGER, NHE3, REQUIRES AN ASSOCIATED REGULATORY PROTEIN

机译：露营介导的上皮刷状鼻NA + / H +交换蛋白NHE3的抑制需要相关的调节蛋白

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摘要

NHE3 is the Na+/H+ exchanger located on the intestinal and renal brush border membrane, where it functions in transepithelial Na+ absorption, Tile brush border Na+ absorptive process is acutely inhibited by activation of cAMP-dependent protein kinase, but the molecular mechanism of this inhibitory effect is poorly understood, We have identified two regulatory proteins, E3KARP and NHERF, that interact with NHE3 to enable cAMP to inhibit NHE3. The twee regulatory proteins are structurally related, sharing approximate to 50% identity In amino acid sequences, It has been previously shown that when NHE3 is transfected into PS120 fibroblasts or Caco-2 cells, cAMP failed to inhibit NHE3 activity, Northern blot analysis showed that both PS120 and Caco-2 cells lacked the expression of both E3KARP and NHERF. In contrast, other cell lines in which cAMP inhibits NHE3, including OK, CHO, and LLC-PK1 cells, expressed NHERF-related regulatory proteins, To determine their functions in cAMP-dependent inhibition of NHE3, E3KARP and NHERF were transfected into PS120/NHE3 fibroblasts. Transfection in PS120/NHE3 fibroblasts with either NHERF or E3KARP reconstituted cAMP-induced induction of NHE3, resulting in 25-30% inhibition in these cells. [References: 35]
机译：NHE3是位于肠和肾刷状边界膜上的Na + / H +交换子，在其上皮细胞Na +吸收中起作用，瓦状刷状边界Na +的吸收过程被cAMP依赖性蛋白激酶的激活强烈抑制，但这种抑制作用的分子机制效果了解甚少，我们已经鉴定出两种调节蛋白，即E3KARP和NHERF，它们与NHE3相互作用，从而使cAMP抑制NHE3。这两个twee调节蛋白在结构上相关，在氨基酸序列中具有大约50％的同一性。以前已经表明，当NHE3转染到PS120成纤维细胞或Caco-2细胞中时，cAMP无法抑制NHE3活性，Northern印迹分析表明PS120和Caco-2细胞均缺乏E3KARP和NHERF的表达。相反，其他cAMP抑制NHE3的细胞系，包括OK，CHO和LLC-PK1细胞，表达了NHERF相关的调节蛋白。为了确定其在cAMP依赖性NHE3依赖性抑制中的功能，E3KARP和NHERF被转染到PS120 / NHE3成纤维细胞。用NHERF或E3KARP在PS120 / NHE3成纤维细胞中转染可重构cAMP诱导的NHE3诱导，导致这些细胞中抑制25-30％。 [参考：35]

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