The protein kinase A-regulated cardiac CI− channel resembles the cystic fibrosis transmembrane conductance regulator

Nature ◽  
1992 ◽  
Vol 360 (6399) ◽  
pp. 81-84 ◽  
Author(s):  
Georg Nagel ◽  
Tzyh-Chang Hwang ◽  
Kent L. Nastiuk ◽  
Angus C. Nairn ◽  
David C. Gadsbyt
Keyword(s):  
Cystic Fibrosis ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Cystic Fibrosis Transmembrane ◽  
Kinase A

Rectal epithelial expression of protein kinase A phosphorylation of cystic fibrosis transmembrane conductance regulator

1994 ◽  
Vol 106 (4) ◽  
pp. 890-898 ◽  
Author(s):  
Mrinalini C. Rao ◽  
Grace B. Bissonnette ◽  
Teresa Mahaffey ◽  
William B. Guggino ◽  
Jay L. Goldstein
Keyword(s):  
Cystic Fibrosis ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Cystic Fibrosis Transmembrane ◽  
Kinase A

scholarly journals β3-Adrenoceptor Control the Cystic Fibrosis Transmembrane Conductance Regulator through a cAMP/Protein Kinase A-independent Pathway

1999 ◽  
Vol 274 (10) ◽  
pp. 6107-6113 ◽  
Author(s):  
Véronique Leblais ◽  
Sophie Demolombe ◽  
Geneviève Vallette ◽  
Dominique Langin ◽  
Isabelle Baró ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Cystic Fibrosis Transmembrane ◽  
Kinase A

scholarly journals Protein kinase A regulates ATP hydrolysis and dimerization by a CFTR (cystic fibrosis transmembrane conductance regulator) domain

2004 ◽  
Vol 378 (1) ◽  
pp. 151-159 ◽  
Author(s):  
L. Daniel HOWELL ◽  
Roy BORCHARDT ◽  
Jolanta KOLE ◽  
Andrew M. KAZ ◽  
Christoph RANDAK ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Protein Kinase ◽  
Fusion Protein ◽  
Protein Kinase A ◽  
Atp Hydrolysis ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Cystic Fibrosis Transmembrane ◽  
Kinase A ◽  
R Domain

Gating of the CFTR Cl− channel is associated with ATP hydrolysis at the nucleotide-binding domains (NBD1, NBD2) and requires PKA (protein kinase A) phosphorylation of the R domain. The manner in which the NBD1, NBD2 and R domains of CFTR (cystic fibrosis transmembrane conductance regulator) interact to achieve a properly regulated ion channel is largely unknown. In this study we used bacterially expressed recombinant proteins to examine interactions between these soluble domains of CFTR in vitro. PKA phosphorylated a fusion protein containing NBD1 and R (NBD1–R–GST) on CFTR residues Ser-660, Ser-700, Ser-712, Ser-737, Ser-768, Ser-795 and Ser-813. Phosphorylation of these serine residues regulated ATP hydrolysis by NBD1–R–GST by increasing the apparent Km for ATP (from 70 to 250 µM) and the Hill coefficient (from 1 to 1.7) without changing the Vmax. When fusion proteins were photolabelled with 8-azido-[α-32P]ATP, PKA phosphorylation increased the apparent kd for nucleotide binding and it caused binding to become co-operative. PKA phosphorylation also resulted in dimerization of NBD1–R–GST but not of R–GST, a related fusion protein lacking the NBD1 domain. Finally, an MBP (maltose-binding protein) fusion protein containing the NBD2 domain (NBD2–MBP) associated with and regulated the ATPase activity of PKA-phosphorylated NBD1–R–GST. Thus when the R domain in NBD1–R–GST is phosphorylated by PKA, ATP binding and hydrolysis becomes co-operative and NBD dimerization occurs. These findings suggest that during the activation of native CFTR, phosphorylation of the R domain by PKA can control the ability of the NBD1 domain to hydrolyse ATP and to interact with other NBD domains.

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