| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-124 |
Sentence |
denotes |
Dynamic regulation of cystic fibrosis transmembrane conductance regulator by competitive interactions of molecular adaptors. |
| T2 |
125-363 |
Sentence |
denotes |
Disorganized ion transport caused by hypo- or hyperfunctioning of the cystic fibrosis transmembrane conductance regulator (CFTR) can be detrimental and may result in life-threatening diseases such as cystic fibrosis or secretory diarrhea. |
| T3 |
364-465 |
Sentence |
denotes |
Thus, CFTR is controlled by elaborate positive and negative regulations for an efficient homeostasis. |
| T4 |
466-625 |
Sentence |
denotes |
It has been shown that expression and activity of CFTR can be regulated either positively or negatively by PDZ (PSD-95/discs large/ZO-1) domain-based adaptors. |
| T5 |
626-856 |
Sentence |
denotes |
Although a positive regulation by PDZ domain-based adaptors such as EBP50/NHERF1 is established, the mechanisms for negative regulation of the CFTR by Shank2, as well as the effects of multiple adaptor interactions, are not known. |
| T6 |
857-1137 |
Sentence |
denotes |
Here we demonstrate a physical and physiological competition between EBP50-CFTR and Shank2-CFTR associations and the dynamic regulation of CFTR activity by these positive and negative interactions using the surface plasmon resonance assays and consecutive patch clamp experiments. |
| T7 |
1138-1410 |
Sentence |
denotes |
Furthermore whereas EBP50 recruits a cAMP-dependent protein kinase (PKA) complex to CFTR, Shank2 was found to be physically and functionally associated with the cyclic nucleotide phosphodiesterase PDE4D that precludes cAMP/PKA signals in epithelial cells and mouse brains. |
| T8 |
1411-1663 |
Sentence |
denotes |
These findings strongly suggest that balanced interactions between the membrane transporter and multiple PDZ-based adaptors play a critical role in the homeostatic regulation of epithelial transport and possibly the membrane transport in other tissues. |
