|
Originally published In Press as doi:10.1074/jbc.M104202200 on August 20, 2001
J. Biol. Chem., Vol. 276, Issue 46, 43239-43245, November 16, 2001
A Molecular Switch for Specific Stimulation of the
BKCa Channel by cGMP and cAMP Kinase*
Xiao-Bo
Zhou ,
Claudia
Arntz§¶,
Simone
Kamm§¶,
Karin
Motejlek ,
Ulrike
Sausbier§,
Ge-Xin
Wang ,
Peter
Ruth§ , and
Michael
Korth
From the Abteilung Pharmakologie für
Pharmazeuten, Universitätsklinikum Hamburg-Eppendorf, Martinistr.
52, D-20246 Hamburg and § Institut für
Pharmakologie und Toxikologie der Technischen Universität
München, Biedersteinerstr. 29, D-80802 München Germany
The cGMP and the cAMP pathways control smooth
muscle tone by regulation of BKCa (BK) channel
activity. BK channels show considerable diversity and plasticity in
their regulation by cyclic nucleotide-dependent protein
kinases. The underlying molecular mechanisms are unclear but may
involve expression of splice variants of the BK channel subunit.
Three isoforms, BKA, BKB, and BKC,
which were cloned from tracheal smooth muscle, differed only in their C
terminus. When expressed in HEK293 cells, cGMP kinase (cGK) but not
cAMP kinase (cAK) stimulated the activity of BKA and
BKB by shifting the voltage dependence of the channel to
more negative potentials. In contrast, BKC was exclusively
stimulated by cAK. BKC lacks a C-terminal tandem
phosphorylation motif for protein kinase C (PKC) with
Ser1151 and Ser1154. Mutation of this motif in
BKA switched channel regulation from cGK to cAK.
Furthermore, inhibition of PKC in excised patches from cells expressing
BKA abolished the stimulatory effect of cGK but allowed
channel stimulation by cAK. cAK and cGK phosphorylated the channel at
different sites. Thus, phosphorylation/dephosphorylation by PKC
determines whether the BK channel is stimulated by cGK or cAK. The
molecular mechanisms may be relevant for smooth muscle relaxation by
cAMP and cGMP.
*
This work was supported by Deutsche Forschungsgemeinschaft.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AY033472 (BKA), AY033473
(BKB), and AY033474 (BKC).
To whom correspondence should be addressed. Tel.:
49-7071-2976781; Fax: 49-7071-292476; E-mail:
peter.ruth@uni-tuebingen.de.
¶
Contributed equally.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.

CiteULike Complore Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
A. Simon, E. O. Harrington, G. X. Liu, G. Koren, and G. Choudhary
Mechanism of C-type natriuretic peptide-induced endothelial cell hyperpolarization
Am J Physiol Lung Cell Mol Physiol,
February 1, 2009;
296(2):
L248 - L256.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Godlewski, L. Offertaler, D. Osei-Hyiaman, F. M. Mo, J. Harvey-White, J. Liu, M. I. Davis, L. Zhang, R. K. Razdan, G. Milman, et al.
The Endogenous Brain Constituent N-Arachidonoyl L-Serine Is an Activator of Large Conductance Ca2+-Activated K+ Channels
J. Pharmacol. Exp. Ther.,
January 1, 2009;
328(1):
351 - 361.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Tian, O. Jeffries, H. McClafferty, A. Molyvdas, I. C. M. Rowe, F. Saleem, L. Chen, J. Greaves, L. H. Chamberlain, H.-G. Knaus, et al.
Palmitoylation gates phosphorylation-dependent regulation of BK potassium channels
PNAS,
December 30, 2008;
105(52):
21006 - 21011.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Estilo, W. Liu, N. Pastor-Soler, P. Mitchell, M. D. Carattino, T. R. Kleyman, and L. M. Satlin
Effect of aldosterone on BK channel expression in mammalian cortical collecting duct
Am J Physiol Renal Physiol,
September 1, 2008;
295(3):
F780 - F788.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
X.-B. Zhou, I. Wulfsen, S. Lutz, E. Utku, U. Sausbier, P. Ruth, T. Wieland, and M. Korth
M2 Muscarinic Receptors Induce Airway Smooth Muscle Activation via a Dual, G{beta}{gamma}-mediated Inhibition of Large Conductance Ca2+-activated K+ Channel Activity
J. Biol. Chem.,
July 25, 2008;
283(30):
21036 - 21044.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. F. King and A. Townsend-Nicholson
Involvement of P2Y1 and P2Y11 Purinoceptors in Parasympathetic Inhibition of Colonic Smooth Muscle
J. Pharmacol. Exp. Ther.,
March 1, 2008;
324(3):
1055 - 1063.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Tian, H. McClafferty, L. Chen, and M. J. Shipston
Reversible Tyrosine Protein Phosphorylation Regulates Large Conductance Voltage- and Calcium-activated Potassium Channels via Cortactin
J. Biol. Chem.,
February 8, 2008;
283(6):
3067 - 3076.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. J. Sanderson, P. Delmotte, Y. Bai, and J. F. Perez-Zogbhi
Regulation of Airway Smooth Muscle Cell Contractility by Ca2+ Signaling and Sensitivity
Proceedings of the ATS,
January 1, 2008;
5(1):
23 - 31.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Zhang, H. H. Patel, F. Murray, C. V. Remillard, C. Schach, P. A. Thistlethwaite, Paul. A. Insel, and J. X.-J. Yuan
Pulmonary artery smooth muscle cells from normal subjects and IPAH patients show divergent cAMP-mediated effects on TRPC expression and capacitative Ca2+ entry
Am J Physiol Lung Cell Mol Physiol,
May 1, 2007;
292(5):
L1202 - L1210.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. K. Isacson, Q. Lu, R. H. Karas, and D. H. Cox
RACK1 is a BKCa channel binding protein
Am J Physiol Cell Physiol,
April 1, 2007;
292(4):
C1459 - C1466.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Magnusson, C. M. Sorensen, T. H. Braunstein, N.-H. Holstein-Rathlou, and M. Salomonsson
Renovascular BKCa channels are not activated in vivo under resting conditions and during agonist stimulation
Am J Physiol Regulatory Integrative Comp Physiol,
January 1, 2007;
292(1):
R345 - R353.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. A. Giembycz and R. Newton
Beyond the dogma: novel {beta}2-adrenoceptor signalling in the airways.
Eur. Respir. J.,
June 1, 2006;
27(6):
1286 - 1306.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. F. Stowe, M. Aldakkak, A. K. S. Camara, M. L. Riess, A. Heinen, S. G. Varadarajan, and M.-T. Jiang
Cardiac mitochondrial preconditioning by Big Ca2+-sensitive K+ channel opening requires superoxide radical generation
Am J Physiol Heart Circ Physiol,
January 1, 2006;
290(1):
H434 - H440.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Zhou, L. Liu, and D. Hu
Involvement of BKCa {alpha} subunit tyrosine phosphorylation in vascular hyporesponsiveness of superior mesenteric artery following hemorrhagic shock in rats
Cardiovasc Res,
November 1, 2005;
68(2):
327 - 335.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Chen, L. Tian, S. H.-F. MacDonald, H. McClafferty, M. S. L. Hammond, J.-M. Huibant, P. Ruth, H.-G. Knaus, and M. J. Shipston
Functionally Diverse Complement of Large Conductance Calcium- and Voltage-activated Potassium Channel (BK) {alpha}-Subunits Generated from a Single Site of Splicing
J. Biol. Chem.,
September 30, 2005;
280(39):
33599 - 33609.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Yang, J. W. Clark, R. M. Bryan, and C. S. Robertson
Mathematical modeling of the nitric oxide/cGMP pathway in the vascular smooth muscle cell
Am J Physiol Heart Circ Physiol,
August 1, 2005;
289(2):
H886 - H897.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Sausbier, C. Arntz, I. Bucurenciu, H. Zhao, X.-B. Zhou, U. Sausbier, S. Feil, S. Kamm, K. Essin, C. A. Sailer, et al.
Elevated Blood Pressure Linked to Primary Hyperaldosteronism and Impaired Vasodilation in BK Channel-Deficient Mice
Circulation,
July 5, 2005;
112(1):
60 - 68.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. M. Brainard, A. J. Miller, J. R. Martens, and S. K. England
Maxi-K channels localize to caveolae in human myometrium: a role for an actin-channel-caveolin complex in the regulation of myometrial smooth muscle K+ current
Am J Physiol Cell Physiol,
July 1, 2005;
289(1):
C49 - C57.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Tian, L. S. Coghill, H. McClafferty, S. H.-F. MacDonald, F. A. Antoni, P. Ruth, H.-G. Knaus, and M. J. Shipston
Distinct stoichiometry of BKCa channel tetramer phosphorylation specifies channel activation and inhibition by cAMP-dependent protein kinase
PNAS,
August 10, 2004;
101(32):
11897 - 11902.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Snellman and S. Nawy
cGMP-Dependent Kinase Regulates Response Sensitivity of the Mouse On Bipolar Cell
J. Neurosci.,
July 21, 2004;
24(29):
6621 - 6628.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. R. Wolfram Kuhlmann, C. Gast, F. Li, M. Schafer, H. Tillmanns, B. Waldecker, and J. Wiecha
Cerivastatin Activates Endothelial Calcium-Activated Potassium Channels and Thereby Modulates Endothelial Nitric Oxide Production and Cell Proliferation
J. Am. Soc. Nephrol.,
April 1, 2004;
15(4):
868 - 875.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. A Widmer, I. C M Rowe, and M. J Shipston
Conditional protein phosphorylation regulates BK channel activity in rat cerebellar Purkinje neurons
J. Physiol.,
October 15, 2003;
552(2):
379 - 391.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. Steffens, X.-B. Zhou, U. Sausbier, C. Sailer, K. Motejlek, P. Ruth, J. Olcese, M. Korth, and T. Wieland
Melatonin Receptor Signaling in Pregnant and Nonpregnant Rat Uterine Myocytes as Probed by Large Conductance Ca2+-Activated K+ Channel Activity
Mol. Endocrinol.,
October 1, 2003;
17(10):
2103 - 2115.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Erxleben, A. L. Everhart, C. Romeo, H. Florance, M. B. Bauer, D. A. Alcorta, S. Rossie, M. J. Shipston, and D. L. Armstrong
Interacting Effects of N-terminal Variation and Strex Exon Splicing on slo Potassium Channel Regulation by Calcium, Phosphorylation, and Oxidation
J. Biol. Chem.,
July 19, 2002;
277(30):
27045 - 27052.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Fury, S. O. Marx, and A. R. Marks
Molecular BKology: The Study of Splicing and Dicing
Sci. Signal.,
March 12, 2002;
2002(123):
pe12 - pe12.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|