|
Originally published In Press as doi:10.1074/jbc.M600433200 on March 22, 2006
J. Biol. Chem., Vol. 281, Issue 20, 14015-14025, May 19, 2006
Integrin Receptor Activation Triggers Converging Regulation of Cav1.2 Calcium Channels by c-Src and Protein Kinase A Pathways*
Peichun Gui ,
Xin Wu ,
Shizhang Ling¶,
Stephanie C. Stotz||1,
Robert J. Winkfein||,
Emily Wilson ,
George E. Davis ,
Andrew P. Braun¶2,
Gerald W. Zamponi||3, and
Michael J. Davis 4
From the
Department of Medical Pharmacology & Physiology, University of Missouri School of Medicine, Columbia, Missouri 65212, the Department of Systems Biology & Translational Medicine, Texas A&M University College of Medicine, College Station, Texas 77840, and the ¶Smooth Muscle and ||Cellular and Molecular Neurobiology Research Groups, University of Calgary School of Medicine, Calgary, Alberta T2N 4N1, Canada
L-type, voltage-gated Ca2+ channels (CaL) play critical roles in brain and muscle cell excitability. Here we show that currents through heterologously expressed neuronal and smooth muscle CaL channel isoforms are acutely potentiated following 5 1 integrin activation. Only the 1C pore-forming channel subunit is critical for this process. Truncation and site-directed mutagenesis strategies reveal that regulation of Cav1.2 by 5 1 integrin requires phosphorylation of 1C C-terminal residues Ser1901 and Tyr2122. These sites are known to be phosphorylated by protein kinase A (PKA) and c-Src, respectively, and are conserved between rat neuronal (Cav1.2c) and smooth muscle (Cav1.2b) isoforms. Kinase assays are consistent with phosphorylation of these two residues by PKA and c-Src. Following 5 1 integrin activation, native CaL channels in rat arteriolar smooth muscle exhibit potentiation that is completely blocked by combined PKA and Src inhibition. Our results demonstrate that integrin-ECM interactions are a common mechanism for the acute regulation of CaL channels in brain and muscle. These findings are consistent with the growing recognition of the importance of integrin-channel interactions in cellular responses to injury and the acute control of synaptic and blood vessel function.
Received for publication, January 17, 2006
, and in revised form, March 10, 2006.
* This work was supported in part by operating grants from the Canadian Institutes of Health Research and the Heart and Stroke Foundation of Alberta and the Northwest Territories (to G. W. Z. and A. P. B.) and National Institutes of Health Grants HL-72989 (to M. J. D.) and RR-017353 to the University of Missouri. The costs of publication of this article were defrayed in part by the payment of page charges. This 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/EBI Data Bank with accession number(s) P22002
[GenBank]
( 1C-c) and P15381
[GenBank]
( 1C-b).
1 Recipient of studentship awards from the Alberta Heritage Foundation for Medical Research and the Canadian Institutes of Health Research.
2 Alberta Heritage Foundation for Medical Research Senior Scholar.
3 Senior Scholar of the Alberta Heritage Foundation for Medical Research and a Canada Research Chair in Molecular Neurobiology.
4 To whom correspondence should be addressed: 1 Hospital Drive, M451, Columbia, MO 65212. Tel.: 573-884-5181; Fax: 573-884-4276; E-mail: davismj{at}health.missouri.edu.

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

|
 |

|
 |
 
S. Dai, D. D. Hall, and J. W. Hell
Supramolecular Assemblies and Localized Regulation of Voltage-Gated Ion Channels
Physiol Rev,
April 1, 2009;
89(2):
411 - 452.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Shi, K. Jian, M. L. Ko, D. Trump, and G. Y.-P. Ko
Retinoschisin, a New Binding Partner for L-type Voltage-gated Calcium Channels in the Retina
J. Biol. Chem.,
February 6, 2009;
284(6):
3966 - 3975.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Lemke, A. Welling, C. J. Christel, A. Blaich, D. Bernhard, P. Lenhardt, F. Hofmann, and S. Moosmang
Unchanged {beta}-Adrenergic Stimulation of Cardiac L-type Calcium Channels in Cav1.2 Phosphorylation Site S1928A Mutant Mice
J. Biol. Chem.,
December 12, 2008;
283(50):
34738 - 34744.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
X. Wu, Y. Yang, P. Gui, Y. Sohma, G. A. Meininger, G. E. Davis, A. P. Braun, and M. J. Davis
Potentiation of large conductance, Ca2+-activated K+ (BK) channels by {alpha}5{beta}1 integrin activation in arteriolar smooth muscle
J. Physiol.,
March 15, 2008;
586(6):
1699 - 1713.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. C. Hocking, P. A. Titus, R. Sumagin, and I. H. Sarelius
Extracellular Matrix Fibronectin Mechanically Couples Skeletal Muscle Contraction With Local Vasodilation
Circ. Res.,
February 15, 2008;
102(3):
372 - 379.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. Alessandri-Haber, O. A. Dina, E. K. Joseph, D. B. Reichling, and J. D. Levine
Interaction of Transient Receptor Potential Vanilloid 4, Integrin, and Src Tyrosine Kinase in Mechanical Hyperalgesia
J. Neurosci.,
January 30, 2008;
28(5):
1046 - 1057.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Ishikawa, Y. Horii, H. Tamura, and S. Shiosaka
Neuropsin (KLK8)-Dependent and -Independent Synaptic Tagging in the Schaffer-Collateral Pathway of Mouse Hippocampus
J. Neurosci.,
January 23, 2008;
28(4):
843 - 849.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Kang, G. R. Ross, and H. I. Akbarali
COOH-terminal association of human smooth muscle calcium channel Cav1.2b with Src kinase protein binding domains: effect of nitrotyrosylation
Am J Physiol Cell Physiol,
December 1, 2007;
293(6):
C1983 - C1990.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Wang, L. M. McNamara, M. B. Schaffler, and S. Weinbaum
A model for the role of integrins in flow induced mechanotransduction in osteocytes
PNAS,
October 2, 2007;
104(40):
15941 - 15946.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Balasubramanian, A. Ahmed, C.-M. Lo, J. S. K. Sham, and K.-P. Yip
Integrin-mediated mechanotransduction in renal vascular smooth muscle cells: activation of calcium sparks
Am J Physiol Regulatory Integrative Comp Physiol,
October 1, 2007;
293(4):
R1586 - R1594.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. R. Ross, M. Kang, N. Shirwany, A. P. Malykhina, M. Drozd, and H. I. Akbarali
Nitrotyrosylation of Ca2+ Channels Prevents c-Src Kinase Regulation of Colonic Smooth Muscle Contractility in Experimental Colitis
J. Pharmacol. Exp. Ther.,
September 1, 2007;
322(3):
948 - 956.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. R. Campbell, J. D. Watkins, K. K. Singh, E. P. Loret, and S. A. Spector
Human Immunodeficiency Virus Type 1 Subtype C Tat Fails To Induce Intracellular Calcium Flux and Induces Reduced Tumor Necrosis Factor Production from Monocytes
J. Virol.,
June 1, 2007;
81(11):
5919 - 5928.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 2006 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|