| Interacting proteins: Q13131 and P13569 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q13131 and P13569 |
Pubmed |
SVM Score :0.0 |
| The interaction is mediated by residues 1420 1457 in CFTR and by the COOH terminal regulatory domain of alpha 1 AMPK . ^^^ GST fusion protein pull down assays in vitro and in transfected cells confirmed the CFTR alpha 1 AMPK interaction and also identified alpha 2 AMPK as an interactor with CFTR . ^^^ AMPK is coexpressed in CFTR expressing cell lines and shares an apical distribution with CFTR in rat nasal epithelium . ^^^ AMPK phosphorylated full length CFTR in vitro , and AMPK coexpression with CFTR in XENOPUS : oocytes inhibited cAMP activated CFTR whole cell Cl ( ) conductance by approximately 35 50 % . ^^^ Because AMPK is a metabolic sensor in cells and responds to changes in cellular ATP , regulation of CFTR by AMPK may be important in inhibiting CFTR under conditions of metabolic stress , thereby linking transepithelial transport to cell metabolic state . . ^^^ |
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| Interacting proteins: Q13131 and P13569 |
Pubmed |
SVM Score :0.0 |
| The metabolic sensor AMP activated kinase ( AMPK ) binds to and phosphorylates CFTR , co localizes with it in various tissues , and inhibits CFTR currents in Xenopus oocytes ( Hallows , K . ^^^ Here we demonstrate that this AMPK CFTR interaction has functional implications in human lung epithelial cells . ^^^ Pharmacologic activation of AMPK inhibited forskolin stimulated CFTR short circuit currents in polarized Calu 3 cell monolayers . ^^^ In whole cell patch clamp experiments , the activation of endogenous AMPK either pharmacologically or by the overexpression of an AMPK activating non catalytic subunit mutant ( AMPK gamma 1 R70Q ) dramatically inhibited forskolin stimulated CFTR conductance in Calu 3 and CFTR expressing Chinese hamster ovary cells . ^^^ Plasma membrane expression of CFTR , assessed by surface biotinylation , was not affected by AMPK activation . ^^^ |
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| Interacting proteins: Q13131 and P13569 |
Pubmed |
SVM Score :0.0 |
| We previously identified the metabolic sensor AMP activated protein kinase ( AMPK ) as a novel protein interacting with CFTR and found that AMPK phosphorylated CFTR and inhibited CFTR dependent whole cell conductances when coexpressed with CFTR in Xenopus oocytes . ^^^ To address the physiological relevance of the CFTR AMPK interaction , we have now studied polarized epithelia and have evaluated the localization of endogenous AMPK and CFTR and measured CFTR activity with modulation of AMPK activity . ^^^ By immunofluorescent imaging , AMPK and CFTR share an overlapping apical distribution in several rat epithelial tissues , including nasopharynx , submandibular gland , pancreas , and ileum . ^^^ CFTR dependent short circuit currents ( 1 ( sc ) ) were measured in polarized T 84 cells grown on permeable supports , and several independent methods were used to modulate endogenous AMPK activity . ^^^ Activation of endogenous AMPK with the cell permeant adenosine analog 5 amino 4 imidazolecarboxamide 1 beta d ribofuranoside ( AICAR ) inhibited forskolin stimulated CFTR dependent 1 ( sc ) in nonpermeabilized monolayers and monolayers with nystatin permeabilization of the basolateral membrane . ^^^ |
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| Interacting proteins: Q13131 and P13569 |
Pubmed |
SVM Score :0.0 |
| Inflamed colons from IL 10 deficient mice exhibited hyporesponsiveness to forskolin stimulation in association with reductions in surface CFTR expression and increased AMPK activity . ^^^ |
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| Interacting proteins: Q13131 and P13569 |
Pubmed |
SVM Score :0.0 |
| RECENT FINDINGS : Recent studies have found that AMPK , which becomes activated during cellular metabolic stress , promotes the cellular uptake of fuel sources such as glucose and fatty acids to promote ATP generation and inhibits ion transport proteins such as the cystic fibrosis transmembrane conductance regulator Cl channel and the epithelial Na channel , thereby limiting the dissipation of transmembrane ion gradients . ^^^ |
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| Interacting proteins: Q13131 and P13569 |
Pubmed |
SVM Score :0.0 |
| AMP activated kinase ( AMPK ) is a ubiquitous metabolic sensor that inhibits the cystic fibrosis ( CF ) transmembrane conductance regulator ( CFTR ) . ^^^ To determine whether CFTR reciprocally regulates AMPK function in airway epithelia and whether such regulation is involved in lung inflammation , AMPK localization , expression , and activity and cellular metabolic profiles were compared as a function of CFTR status in CF and non CF primary human bronchial epithelial ( HBE ) cells . ^^^ As compared with non CF HBE cells , CF cells had greater and more diffuse AMPK staining and had greater AMPK activity than their morphologically matched non CF counterparts . ^^^ The cellular [ AMP ] / [ ATP ] ratio was higher in undifferentiated than in differentiated non CF cells , which correlated with AMPK activity under these conditions . ^^^ However , this nucleotide ratio did not predict AMPK activity in differentiating CF cells . ^^^ |
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| Interacting proteins: Q13131 and P13569 |
Pubmed |
SVM Score :0.0 |
| The AMP activated protein kinase ( AMPK ) is a heterotrimer composed of different isoforms of the alphabetagamma subunits , where the alpha 1 catalytic subunit binds CFTR . ^^^ 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 ( NBD 1 ) and AMPK alpha 1 binds the second ( NBD 2 ) 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 gamma1 . . ^^^ |
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