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NDPK-A (but not NDPK-B) and AMPK alpha 1 (but not AMPK alpha 2) bind the cystic fibrosis transmembrane conductance regulator in epithelial cell membranes

机译：NDPK-A（但不是NDPK-B）和AMPK alpha 1（但不是AMPK alpha 2）结合上皮细胞膜中的囊性纤维化跨膜电导调节剂

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摘要

Cystic fibrosis (CF) results from mutations within the cystic fibrosis transmembrane-conductance regulator (CFTR) protein. The AMP-activated protein kinase (AMPK) is a heterotrimer composed of different isoforms of the alpha beta gamma subunits, where the alpha 1 catalytic subunit binds CFTR. Nucleoside diphosphate kinase (NDPK, NM23/awd) converts nucleoside diphosphates to nucleoside triphosphates but also acts as a protein kinase. We recently showed that AMPK alpha 1 binds NDPK-A in lung epithelial cytosol. Here we report that in the plasma membrane of human airway epithelial cells, NDPK-A and AMPK alpha 1 associate with the plasma membrane via CFTR. We show that the regulatory domain of CFTR binds NDPK-A whereas AMPK gamma 1 or gamma 2 bind the first nucleotide binding domain (NBD1) and AMPK alpha 1 binds the second (NBD2) of CFTR. We also show that NDPK-A specifically binds AMPK alpha 1 and AMPK gamma 2 subunits, thereby specifying the isozyme of AMPK heterotrimer that associates with CFTR at the membrane. Thus, the combined data provide novel insight into the subunit composition of the epithelial CFTR/AMPK/NDPK complex, such that: CFTR interacts specifically with AMPK alpha 1, gamma 2 and NDPK-A and not NDPK-B or AMPK gamma 1. (c) 2006 Elsevier Inc. All rights reserved.
机译：囊性纤维化（CF）是由囊性纤维化跨膜电导调节剂（CFTR）蛋白内的突变引起的。 AMP激活的蛋白激酶（AMPK）是由三类不同的异构体组成的异源三聚体，其中α1催化亚基与CFTR结合。核苷二磷酸激酶（NDPK，NM23 / awd）可将核苷二磷酸转化为核苷三磷酸，但也可作为蛋白激酶。我们最近显示，AMPK alpha 1结合肺上皮细胞溶胶中的NDPK-A。在这里，我们报道在人气道上皮细胞的质膜中，NDPK-A和AMPK alpha 1通过CFTR与质膜结合。我们显示CFTR的调节域结合NDPK-A，而AMPKγ1或γ2结合第一个核苷酸结合域（NBD1），而AMPKα1结合第二个CFTR（NBD2）。我们还显示，NDPK-A特异性结合AMPK alpha 1和AMPKγ2亚基，从而指定了与膜上CFTR相关的AMPK异三聚体的同工酶。因此，合并后的数据为上皮CFTR / AMPK / NDPK复合物的亚基组成提供了新颖的见解，使得：CFTR与AMPKα1，γ2和NDPK-A特异性相互作用，而不与NDPK-B或AMPKγ1相互作用。（ c）2006 Elsevier Inc.保留所有权利。

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