|
J Biol Chem, Vol. 275, Issue 8, 5504-5511, February 25, 2000
Cysteine-rich Protein 2, a Novel Substrate for cGMP Kinase I in
Enteric Neurons and Intestinal Smooth Muscle*
Andrea
Huber ,
Winfried L.
Neuhuber§,
Norbert
Klugbauer¶,
Peter
Ruth¶ , and
Hans-Dieter
Allescher
From the II. Medizinische Klinik und Poliklinik,
Technische Universität München, D-81675 München,
Germany, the § Institut für Anatomie,
Universität Erlangen, D-91054 Erlangen, Germany, and the
¶ Institut für Pharmakologie und Toxikologie, Technische
Universität München, D-80802 München, Germany
Nitric oxide/cGMP/cGMP kinase I (cGKI) signaling
causes relaxation of intestinal smooth muscle. In the gastrointestinal
tract substrates of cGKI have not been identified yet. In the present study a protein interacting with cGKI has been isolated from a rat
intestinal cDNA library using the yeast two-hybrid system. The
protein was identified as cysteine-rich protein 2 (CRP2), recently
cloned from rat brain (Okano, I., Yamamoto, T., Kaji, A., Kimura, T.,
Mizuno, K., and Nakamura, T. (1993) FEBS Lett. 333, 51-55). Recombinant CRP2 is specifically phosphorylated by cGKs but
not by cAMP kinase in vitro. Co-transfection of CRP2 and
cGKI into COS cells confirmed the phosphorylation of CRP2 in
vivo. Cyclic GMP kinase I phosphorylated CRP2 at Ser-104, because the mutation to Ala completely prevented the in vivo
phosphorylation. Immunohistochemical analysis using confocal laser scan
microscopy showed a co-localization of CRP2 and cGKI in the inner part
of the circular muscle layer, in the muscularis mucosae, and in
specific neurons of the myenteric and submucosal plexus. The
co-localization together with the specific phosphorylation of CRP2 by
cGKI in vitro and in vivo suggests that CRP2 is
a novel substrate of cGKI in neurons and smooth muscle of the small intestine.
*
This work was supported by Grant SFB 391 from the Deutsche
Forschungsgemeinschaft (to H. D. A. and P. R.) and
Kommission für Klinische Forschung Grant TU Munich F71-98 (to
H. D. A.).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.
To whom correspondence should be addressed: Inst. für
Pharmakologie und Toxikologie, Biedersteinerstr. 29, D-80802
München, Germany. Tel.: 49-89-4140-3265; Fax: 49-89-4140-3261;
E-mail: ruth@ipt.med.tu-muenchen.de.
Copyright © 2000 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. Schmidtko, W. Gao, M. Sausbier, I. Rauhmeier, U. Sausbier, E. Niederberger, K. Scholich, A. Huber, W. Neuhuber, H.-D. Allescher, et al.
Cysteine-Rich Protein 2, a Novel Downstream Effector of cGMP/cGMP-Dependent Protein Kinase I-Mediated Persistent Inflammatory Pain
J. Neurosci.,
February 6, 2008;
28(6):
1320 - 1330.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Zhang, S. Zhuang, D. E. Casteel, D. J. Looney, G. R. Boss, and R. B. Pilz
A Cysteine-rich LIM-only Protein Mediates Regulation of Smooth Muscle-specific Gene Expression by cGMP-dependent Protein Kinase
J. Biol. Chem.,
November 16, 2007;
282(46):
33367 - 33380.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. F. Chang, N. S. Belaguli, J. Chang, and R. J. Schwartz
LIM-only protein, CRP2, switched on smooth muscle gene activity in adult cardiac myocytes
PNAS,
January 2, 2007;
104(1):
157 - 162.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. Hofmann, R. Feil, T. Kleppisch, and J. Schlossmann
Function of cGMP-Dependent Protein Kinases as Revealed by Gene Deletion
Physiol Rev,
January 1, 2006;
86(1):
1 - 23.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. E. Casteel, G. R. Boss, and R. B. Pilz
Identification of the Interface between cGMP-dependent Protein Kinase I{beta} and Its Interaction Partners TFII-I and IRAG Reveals a Common Interaction Motif
J. Biol. Chem.,
November 18, 2005;
280(46):
38211 - 38218.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
I. Tegeder, D. Del Turco, A. Schmidtko, M. Sausbier, R. Feil, F. Hofmann, T. Deller, P. Ruth, and G. Geisslinger
Reduced inflammatory hyperalgesia with preservation of acute thermal nociception in mice lacking cGMP-dependent protein kinase I
PNAS,
March 2, 2004;
101(9):
3253 - 3257.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. I. Dorrell, E. Aguilar, C. Weber, and M. Friedlander
Global Gene Expression Analysis of the Developing Postnatal Mouse Retina
Invest. Ophthalmol. Vis. Sci.,
March 1, 2004;
45(3):
1009 - 1019.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. Butt, S. Gambaryan, N. Gottfert, A. Galler, K. Marcus, and H. E. Meyer
Actin Binding of Human LIM and SH3 Protein Is Regulated by cGMP- and cAMP-dependent Protein Kinase Phosphorylation on Serine 146
J. Biol. Chem.,
April 25, 2003;
278(18):
15601 - 15607.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Schmidt, M. Werner, P. A. Heppenstall, M. Henning, M. I. More, S. Kuhbandner, G. R. Lewin, F. Hofmann, R. Feil, and F. G. Rathjen
cGMP-mediated signaling via cGKI{alpha} is required for the guidance and connectivity of sensory axons
J. Cell Biol.,
November 7, 2002;
159(3):
489 - 498.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. McLoughlin, E. Ehler, G. Carlile, J. D. Licht, and B. W. Schafer
The LIM-only Protein DRAL/FHL2 Interacts with and Is a Corepressor for the Promyelocytic Leukemia Zinc Finger Protein
J. Biol. Chem.,
September 27, 2002;
277(40):
37045 - 37053.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. E. Casteel, S. Zhuang, T. Gudi, J. Tang, M. Vuica, S. Desiderio, and R. B. Pilz
cGMP-dependent Protein Kinase Ibeta Physically and Functionally Interacts with the Transcriptional Regulator TFII-I
J. Biol. Chem.,
August 23, 2002;
277(35):
32003 - 32014.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Ammendola, A. Geiselhoringer, F. Hofmann, and J. Schlossmann
Molecular Determinants of the Interaction between the Inositol 1,4,5-Trisphosphate Receptor-associated cGMP Kinase Substrate (IRAG) and cGMP Kinase Ibeta
J. Biol. Chem.,
June 22, 2001;
276(26):
24153 - 24159.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Saur, W. L. Neuhuber, B. Gengenbach, A. Huber, V. Schusdziarra, and H.-D. Allescher
Site-specific gene expression of nNOS variants in distinct functional regions of rat gastrointestinal tract
Am J Physiol Gastrointest Liver Physiol,
February 1, 2002;
282(2):
G349 - G358.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 2000 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|