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Role of binding and nucleoside diphosphate kinase A in the regulation of the cystic fibrosis transmembrane conductance regulator by AMP-activated protein kinase

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Role of binding and nucleoside diphosphate kinase A in the regulation of the cystic fibrosis transmembrane conductance regulator by AMP-activated protein kinase. / King, J Darwin; Lee, Jeffrey; Riemen, Claudia E; Neumann, Dietbert; Xiong, Sheng; Foskett, J Kevin; Mehta, Anil; Muimo, Richmond; Hallows, Kenneth R.

In: Journal of Biological Chemistry, Vol. 287, No. 40, 2012, p. 33389-33400.

Research output: Contribution to journalArticle

Harvard

King, JD, Lee, J, Riemen, CE, Neumann, D, Xiong, S, Foskett, JK, Mehta, A, Muimo, R & Hallows, KR 2012, 'Role of binding and nucleoside diphosphate kinase A in the regulation of the cystic fibrosis transmembrane conductance regulator by AMP-activated protein kinase' Journal of Biological Chemistry, vol 287, no. 40, pp. 33389-33400.

APA

King, J. D., Lee, J., Riemen, C. E., Neumann, D., Xiong, S., Foskett, J. K., Mehta, A., Muimo, R., & Hallows, K. R. (2012). Role of binding and nucleoside diphosphate kinase A in the regulation of the cystic fibrosis transmembrane conductance regulator by AMP-activated protein kinase. Journal of Biological Chemistry, 287(40), 33389-33400doi: 10.1074/jbc.M112.396036

Vancouver

King JD, Lee J, Riemen CE, Neumann D, Xiong S, Foskett JK et al. Role of binding and nucleoside diphosphate kinase A in the regulation of the cystic fibrosis transmembrane conductance regulator by AMP-activated protein kinase. Journal of Biological Chemistry. 2012;287(40):33389-33400.

Author

King, J Darwin; Lee, Jeffrey; Riemen, Claudia E; Neumann, Dietbert; Xiong, Sheng; Foskett, J Kevin; Mehta, Anil; Muimo, Richmond; Hallows, Kenneth R / Role of binding and nucleoside diphosphate kinase A in the regulation of the cystic fibrosis transmembrane conductance regulator by AMP-activated protein kinase.

In: Journal of Biological Chemistry, Vol. 287, No. 40, 2012, p. 33389-33400.

Research output: Contribution to journalArticle

Bibtex - Download

@article{d548935c6cec4a4cad39d1b9c5cd153f,
title = "Role of binding and nucleoside diphosphate kinase A in the regulation of the cystic fibrosis transmembrane conductance regulator by AMP-activated protein kinase",
author = "King, {J Darwin} and Jeffrey Lee and Riemen, {Claudia E} and Dietbert Neumann and Sheng Xiong and Foskett, {J Kevin} and Anil Mehta and Richmond Muimo and Hallows, {Kenneth R}",
year = "2012",
volume = "287",
number = "40",
pages = "33389--33400",
journal = "Journal of Biological Chemistry",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Role of binding and nucleoside diphosphate kinase A in the regulation of the cystic fibrosis transmembrane conductance regulator by AMP-activated protein kinase

A1 - King,J Darwin

A1 - Lee,Jeffrey

A1 - Riemen,Claudia E

A1 - Neumann,Dietbert

A1 - Xiong,Sheng

A1 - Foskett,J Kevin

A1 - Mehta,Anil

A1 - Muimo,Richmond

A1 - Hallows,Kenneth R

AU - King,J Darwin

AU - Lee,Jeffrey

AU - Riemen,Claudia E

AU - Neumann,Dietbert

AU - Xiong,Sheng

AU - Foskett,J Kevin

AU - Mehta,Anil

AU - Muimo,Richmond

AU - Hallows,Kenneth R

PY - 2012

Y1 - 2012

N2 - Cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel mutations cause cystic fibrosis lung disease. A better understanding of CFTR regulatory mechanisms could suggest new therapeutic strategies. AMP-activated protein kinase (AMPK) binds to and phosphorylates CFTR, attenuating PKA-activated CFTR gating. However, the requirement for AMPK binding to CFTR and the potential role of other proteins in this regulation are unclear. We report that nucleoside diphosphate kinase A (NDPK-A) interacts with both AMPK and CFTR in overlay blots of airway epithelial cell lysates. Binding studies in Xenopus oocytes and transfected HEK-293 cells revealed that a CFTR peptide fragment that binds AMPK (CFTR-1420-57) disrupted the AMPK-CFTR interaction. Introduction of CFTR-1420-57 into human bronchial Calu-3 cells enhanced forskolin-stimulated whole cell conductance in patch clamp measurements. Similarly, injection of CFTR-1420-57 into Xenopus oocytes blocked the inhibition of cAMP-stimulated CFTR conductance by AMPK in two-electrode voltage clamp studies. AMPK also inhibited CFTR conductance with co-expression of WT NDPK-A in two-electrode voltage clamp studies, but co-expression of a catalytically inactive H118F mutant or various Ser-120 NDPK-A mutants prevented this inhibition. In vitro phosphorylation of WT NDPK-A was enhanced by purified active AMPK, but phosphorylation was prevented in H118F and phosphomimic Ser-120 NDPK-A mutants. AMPK does not appear to phosphorylate NDPK-A directly but rather promotes an NDPK-A autophosphorylation event that involves His-118 and Ser-120. Taken together, these results suggest that NDPK-A exists in a functional cellular complex with AMPK and CFTR in airway epithelia, and NDPK-A catalytic function is required for the AMPK-dependent regulation of CFTR.

AB - Cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel mutations cause cystic fibrosis lung disease. A better understanding of CFTR regulatory mechanisms could suggest new therapeutic strategies. AMP-activated protein kinase (AMPK) binds to and phosphorylates CFTR, attenuating PKA-activated CFTR gating. However, the requirement for AMPK binding to CFTR and the potential role of other proteins in this regulation are unclear. We report that nucleoside diphosphate kinase A (NDPK-A) interacts with both AMPK and CFTR in overlay blots of airway epithelial cell lysates. Binding studies in Xenopus oocytes and transfected HEK-293 cells revealed that a CFTR peptide fragment that binds AMPK (CFTR-1420-57) disrupted the AMPK-CFTR interaction. Introduction of CFTR-1420-57 into human bronchial Calu-3 cells enhanced forskolin-stimulated whole cell conductance in patch clamp measurements. Similarly, injection of CFTR-1420-57 into Xenopus oocytes blocked the inhibition of cAMP-stimulated CFTR conductance by AMPK in two-electrode voltage clamp studies. AMPK also inhibited CFTR conductance with co-expression of WT NDPK-A in two-electrode voltage clamp studies, but co-expression of a catalytically inactive H118F mutant or various Ser-120 NDPK-A mutants prevented this inhibition. In vitro phosphorylation of WT NDPK-A was enhanced by purified active AMPK, but phosphorylation was prevented in H118F and phosphomimic Ser-120 NDPK-A mutants. AMPK does not appear to phosphorylate NDPK-A directly but rather promotes an NDPK-A autophosphorylation event that involves His-118 and Ser-120. Taken together, these results suggest that NDPK-A exists in a functional cellular complex with AMPK and CFTR in airway epithelia, and NDPK-A catalytic function is required for the AMPK-dependent regulation of CFTR.

U2 - 10.1074/jbc.M112.396036

DO - 10.1074/jbc.M112.396036

M1 - Article

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 40

VL - 287

SP - 33389

EP - 33400

ER -

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