|
Volume 272, Number 36,
Issue of September 5, 1997
pp. 22824-22831
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
Tyrosine Phosphorylation of Connexin 43 by v-Src Is Mediated by
SH2 and SH3 Domain Interactions
(Received for publication, April 30, 1997, and in revised form, June 10, 1997)
Martha Y.
Kanemitsu
,
Lenora W. M.
Loo
§
,
Suzanne
Simon
,
Alan F.
Lau
§
and
Walter
Eckhart
From the Molecular Biology and Virology Laboratory,
The Salk Institute for Biological Studies, La Jolla, California 92037 and § Molecular Carcinogenesis, Cancer Research Center of
Hawaii, University of Hawaii at Manoa, Honolulu, Hawaii 96813
Reduction of gap junctional communication in
v-src transformed cells is accompanied by tyrosine
phosphorylation of the gap junction protein, connexin 43 (Cx43). Cx43
is phosphorylated on tyrosine by v-Src. The Src homology 3 (SH3) and
Src homology 2 (SH2) domains of v-Src mediate interactions with
substrate proteins. SH3 domains interact with proline-rich peptide
motifs. SH2 domains associate with short amino acid sequences
containing phosphotyrosine. We present evidence that the SH3 and SH2
domains of v-Src bind to proline-rich motifs and a phosphorylated
tyrosine residue in the C-terminal tail of Cx43. Cx43 bound to the SH3
domain of v-Src, but not c-Src, in vitro.
Tyrosine-phosphorylated Cx43 bound to the SH2 domain of v-Src in
vitro. v-Src coprecipitated with Cx43 from
v-src-transformed Rat-1 fibroblasts. Mutations in the SH3 and SH2 domains of v-Src, and in the proline-rich region or tyrosine 265 of Cx43, reduced interactions between v-Src and Cx43 in
vivo. Tyrosine phosphorylation of Cx43 was dependent on the
association of v-Src and Cx43. These results provide further evidence
for the direct involvement of v-Src in tyrosine phosphorylation of Cx43
and inhibition of gap junctional communication in
v-src-transformed cells.

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

|
 |

|
 |
 
P. Gong, D. J. Angelini, S. Yang, G. Xia, A. S. Cross, D. Mann, D. D. Bannerman, S. N. Vogel, and S. E. Goldblum
TLR4 Signaling Is Coupled to SRC Family Kinase Activation, Tyrosine Phosphorylation of Zonula Adherens Proteins, and Opening of the Paracellular Pathway in Human Lung Microvascular Endothelia
J. Biol. Chem.,
May 9, 2008;
283(19):
13437 - 13449.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. J. Martin and A. S. Prince
TLR2 Regulates Gap Junction Intercellular Communication in Airway Cells
J. Immunol.,
April 1, 2008;
180(7):
4986 - 4993.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Shen, P. R. Khusial, X. Li, H. Ichikawa, A. P. Moreno, and G. S. Goldberg
Src Utilizes Cas to Block Gap Junctional Communication Mediated by Connexin43
J. Biol. Chem.,
June 29, 2007;
282(26):
18914 - 18921.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. De Vuyst, E. Decrock, M. De Bock, H. Yamasaki, C. C. Naus, W. H. Evans, and L. Leybaert
Connexin Hemichannels and Gap Junction Channels Are Differentially Influenced by Lipopolysaccharide and Basic Fibroblast Growth Factor
Mol. Biol. Cell,
January 1, 2007;
18(1):
34 - 46.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. E. Isakson, G. Kronke, A. Kadl, N. Leitinger, and B. R. Duling
Oxidized Phospholipids Alter Vascular Connexin Expression, Phosphorylation, and Heterocellular Communication
Arterioscler. Thromb. Vasc. Biol.,
October 1, 2006;
26(10):
2216 - 2221.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. F. Lau
c-Src: Bridging the Gap Between Phosphorylation- and Acidification-Induced Gap Junction Channel Closure
Sci. Signal.,
July 5, 2005;
2005(291):
pe33 - pe33.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Aravindakshan and D. G. Cyr
Nonylphenol Alters Connexin 43 Levels and Connexin 43 Phosphorylation Via an Inhibition of the p38-Mitogen-Activated Protein Kinase Pathway
Biol Reprod,
May 1, 2005;
72(5):
1232 - 1240.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. I. Plotkin, J. I. Aguirre, S. Kousteni, S. C. Manolagas, and T. Bellido
Bisphosphonates and Estrogens Inhibit Osteocyte Apoptosis via Distinct Molecular Mechanisms Downstream of Extracellular Signal-regulated Kinase Activation
J. Biol. Chem.,
February 25, 2005;
280(8):
7317 - 7325.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. L. Sorgen, H. S. Duffy, P. Sahoo, W. Coombs, M. Delmar, and D. C. Spray
Structural Changes in the Carboxyl Terminus of the Gap Junction Protein Connexin43 Indicates Signaling between Binding Domains for c-Src and Zonula Occludens-1
J. Biol. Chem.,
December 24, 2004;
279(52):
54695 - 54701.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. T. Fu, J. F. Bechberger, M. A. Ozog, B. Perbal, and C. C. Naus
CCN3 (NOV) Interacts with Connexin43 in C6 Glioma Cells: POSSIBLE MECHANISM OF CONNEXIN-MEDIATED GROWTH SUPPRESSION
J. Biol. Chem.,
August 27, 2004;
279(35):
36943 - 36950.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Seki, H. S. Duffy, W. Coombs, D. C. Spray, S. M. Taffet, and M. Delmar
Modifications in the Biophysical Properties of Connexin43 Channels by a Peptide of the Cytoplasmic Loop Region
Circ. Res.,
August 20, 2004;
95(4):
e22 - e28.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. N.G Giepmans
Gap junctions and connexin-interacting proteins
Cardiovasc Res,
May 1, 2004;
62(2):
233 - 245.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. C. SAEZ, V. M. BERTHOUD, M. C. BRANES, A. D. MARTINEZ, and E. C. BEYER
Plasma Membrane Channels Formed by Connexins: Their Regulation and Functions
Physiol Rev,
October 1, 2003;
83(4):
1359 - 1400.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. J. Cameron, S. Malik, M. Akaike, N. Lerner-Marmarosh, C. Yan, J.-D. Lee, J.-i. Abe, and J. Yang
Regulation of Epidermal Growth Factor-induced Connexin 43 Gap Junction Communication by Big Mitogen-activated Protein Kinase 1/ERK5 but Not ERK1/2 Kinase Activation
J. Biol. Chem.,
May 9, 2003;
278(20):
18682 - 18688.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Huang, T. Dudez, I. Scerri, M. A. Thomas, B. N. G. Giepmans, S. Suter, and M. Chanson
Defective Activation of c-Src in Cystic Fibrosis Airway Epithelial Cells Results in Loss of Tumor Necrosis Factor-alpha -induced Gap Junction Regulation
J. Biol. Chem.,
February 28, 2003;
278(10):
8326 - 8332.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. T. Cottrell, R. Lin, B. J. Warn-Cramer, A. F. Lau, and J. M. Burt
Mechanism of v-Src- and mitogen-activated protein kinase-induced reduction of gap junction communication
Am J Physiol Cell Physiol,
February 1, 2003;
284(2):
C511 - C520.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. Oviedo-Orta and W. H. Evans
Gap junctions and connexins: potential contributors to the immunological synapse
J. Leukoc. Biol.,
October 1, 2002;
72(4):
636 - 642.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. N. Nitabach, D. A. Llamas, I. J. Thompson, K. A. Collins, and T. C. Holmes
Phosphorylation-Dependent and Phosphorylation-Independent Modes of Modulation of Shaker Family Voltage-Gated Potassium Channels by Src Family Protein Tyrosine Kinases
J. Neurosci.,
September 15, 2002;
22(18):
7913 - 7922.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. R. Hauck, D. A. Hsia, D. Ilic, and D. D. Schlaepfer
v-Src SH3-enhanced Interaction with Focal Adhesion Kinase at beta 1 Integrin-containing Invadopodia Promotes Cell Invasion
J. Biol. Chem.,
April 5, 2002;
277(15):
12487 - 12490.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. M. Yanochko and A. J. Yool
Regulated Cationic Channel Function in Xenopus Oocytes Expressing Drosophila Big Brain
J. Neurosci.,
April 1, 2002;
22(7):
2530 - 2540.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. P. Moreno, M. Chanson, J. Anumonwo, I. Scerri, H. Gu, S. M. Taffet, and M. Delmar
Role of the Carboxyl Terminal of Connexin43 in Transjunctional Fast Voltage Gating
Circ. Res.,
March 8, 2002;
90(4):
450 - 457.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. I. Plotkin, S. C. Manolagas, and T. Bellido
Transduction of Cell Survival Signals by Connexin-43 Hemichannels
J. Biol. Chem.,
March 1, 2002;
277(10):
8648 - 8657.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
I. Granot, E. Bechor, A. Barash, and N. Dekel
Connexin43 in Rat Oocytes: Developmental Modulation of Its Phosphorylation
Biol Reprod,
March 1, 2002;
66(3):
568 - 573.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Lin, B. J. Warn-Cramer, W. E. Kurata, and A. F. Lau
v-Src phosphorylation of connexin 43 on Tyr247 and Tyr265 disrupts gap junctional communication
J. Cell Biol.,
August 20, 2001;
154(4):
815 - 828.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Nars and M. Vihinen
Coevolution of the Domains of Cytoplasmic Tyrosine Kinases
Mol. Biol. Evol.,
March 1, 2001;
18(3):
312 - 321.
[Abstract]
[Full Text]
|
 |
|

|
 |

|
 |
 
M. N. Nitabach, D. A. Llamas, R. C. Araneda, J. L. Intile, I. J. Thompson, Y. I. Zhou, and T. C. Holmes
A mechanism for combinatorial regulation of electrical activity: Potassium channel subunits capable of functioning as Src homology 3-dependent adaptors
PNAS,
January 5, 2001;
(2001)
31446198.
[Abstract]
[Full Text]
|
 |
|

|
 |

|
 |
 
S Suarez and K Ballmer-Hofer
VEGF transiently disrupts gap junctional communication in endothelial cells
J. Cell Sci.,
January 3, 2001;
114(6):
1229 - 1235.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Z. Hossain, A. B. Jagdale, P. Ao, A. Kazlauskas, and A. L. Boynton
Disruption of Gap Junctional Communication by the Platelet-derived Growth Factor Is Mediated via Multiple Signaling Pathways
J. Biol. Chem.,
April 9, 1999;
274(15):
10489 - 10496.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Zhou, E. M. Kasperek, and B. J. Nicholson
Dissection of the Molecular Basis of pp60v-src Induced Gating of Connexin 43 Gap Junction Channels
J. Cell Biol.,
March 8, 1999;
144(5):
1033 - 1045.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Calero, M. Kanemitsu, S. M. Taffet, A. F. Lau, and M. Delmar
A 17mer Peptide Interferes With Acidification-Induced Uncoupling of Connexin43
Circ. Res.,
May 19, 1998;
82(9):
929 - 935.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Toyofuku, Y. Akamatsu, H. Zhang, T. Kuzuya, M. Tada, and M. Hori
c-Src Regulates the Interaction between Connexin-43 and ZO-1 in Cardiac Myocytes
J. Biol. Chem.,
January 12, 2001;
276(3):
1780 - 1788.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. N. G. Giepmans, T. Hengeveld, F. R. Postma, and W. H. Moolenaar
Interaction of c-Src with Gap Junction Protein Connexin-43. ROLE IN THE REGULATION OF CELL-CELL COMMUNICATION
J. Biol. Chem.,
March 9, 2001;
276(11):
8544 - 8549.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. R. Hauck, T. Hunter, and D. D. Schlaepfer
The v-Src SH3 Domain Facilitates a Cell Adhesion-independent Association with Focal Adhesion Kinase
J. Biol. Chem.,
May 18, 2001;
276(21):
17653 - 17662.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. N. Nitabach, D. A. Llamas, R. C. Araneda, J. L. Intile, I. J. Thompson, Y. I. Zhou, and T. C. Holmes
A mechanism for combinatorial regulation of electrical activity: Potassium channel subunits capable of functioning as Src homology 3-dependent adaptors
PNAS,
January 16, 2001;
98(2):
705 - 710.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. P. Moreno, M. Chanson, J. Anumonwo, I. Scerri, H. Gu, S. M. Taffet, and M. Delmar
Role of the Carboxyl Terminal of Connexin43 in Transjunctional Fast Voltage Gating
Circ. Res.,
March 8, 2002;
90(4):
450 - 457.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 1997 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|