|
Volume 271, Number 43,
Issue of October 25, 1996
pp. 26588-26595
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
Phosphatidylinositol 3-Kinase Mediates the Inhibitory Effect
of Epidermal Growth Factor on Calcium-dependent
Chloride Secretion
(Received for publication, June 20, 1996, and in revised form, August 7, 1996)
Jorge M.
Uribe
,
Stephen J.
Keely
,
Alexis E.
Traynor-Kaplan
and
Kim E.
Barrett
From the Department of Medicine, University of California, San
Diego, School of Medicine, San Diego, California 92103
Epidermal growth factor (EGF) and carbachol both
inhibit calcium-activated chloride secretion by the human colonic
epithelial cell line, T84. Although the inhibitory
mechanism for the carbachol effect involves the 3,4,5,6-isomer of
inositol tetrakisphosphate, the mechanisms responsible for the EGF
effect have not yet been fully elucidated. Here, we studied the role of
phosphatidylinositol 3-kinase (PI 3-kinase) in the inhibitory
effect of EGF. The PI 3-kinase inhibitor, wortmannin, slightly
increased basal chloride secretion and potentiated the secretory
response to thapsigargin. Wortmannin also partially reversed
EGF-induced, but not carbachol-induced, inhibition of
thapsigargin-stimulated chloride secretion. Wortmannin alone had no
effect on carbachol- or histamine-induced chloride secretion and
completely reversed EGF-induced inhibition of the secretory response to
these agonists. EGF, carbachol, histamine, and thapsigargin all
increased levels of the 85-kDa regulatory subunit of PI 3-kinase in
antiphosphotyrosine immunoprecipitates. However, only EGF
significantly increased levels of the 110-kDa catalytic
subunit. Furthermore, only EGF increased PI 3-kinase activity in an
in vitro kinase assay. High levels of
phosphatidylinositol ()-monophosphate were present in unstimulated
cells and significantly reduced by wortmannin. EGF, but not carbachol,
rapidly increased levels of phosphatidylinositol (3,4)-bisphosphate
and phosphatidylinositol (3,4,5)-trisphosphate. Production of these
lipids was also sensitive to wortmannin. Our data suggest that EGF
activates PI 3-kinase and that its lipid products may mediate the
inhibitory effect of EGF on calcium-dependent chloride
secretion. Our data also suggest that a phosphatidylinositol-specific
3-kinase activity is present in unstimulated T84 cells and
may regulate production of phosphatidylinositol ()-monophosphate and
basal secretory tone.

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

|
 |

|
 |
 
C. Deachapunya, S. Poonyachoti, and N. Krishnamra
Regulation of electrolyte transport across cultured endometrial epithelial cells by prolactin
J. Endocrinol.,
June 1, 2008;
197(3):
575 - 582.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. E. Chappell, M. Bunz, E. Smoll, H. Dong, C. Lytle, K. E. Barrett, and D. F. McCole
Hydrogen peroxide inhibits Ca2+-dependent chloride secretion across colonic epithelial cells via distinct kinase signaling pathways and ion transport proteins
FASEB J,
June 1, 2008;
22(6):
2023 - 2036.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. O'Mahony, F. Toumi, M. S. Mroz, G. Ferguson, and S. J. Keely
Induction of Na+/K+/2Cl- cotransporter expression mediates chronic potentiation of intestinal epithelial Cl- secretion by EGF
Am J Physiol Cell Physiol,
June 1, 2008;
294(6):
C1362 - C1370.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. E. Barrett
New ways of thinking about (and teaching about) intestinal epithelial function
Advan Physiol Educ,
March 1, 2008;
32(1):
25 - 34.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. F. McCole, A. Truong, M. Bunz, and K. E. Barrett
Consequences of Direct Versus Indirect Activation of Epidermal Growth Factor Receptor in Intestinal Epithelial Cells Are Dictated by Protein-tyrosine Phosphatase 1B
J. Biol. Chem.,
May 4, 2007;
282(18):
13303 - 13315.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Y. C. Chow and K. E. Barrett
Role of protein phosphatase 2A in calcium-dependent chloride secretion by human colonic epithelial cells
Am J Physiol Cell Physiol,
January 1, 2007;
292(1):
C452 - C459.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. S. Bertelsen, G. Paesold, S. L. Marcus, B. B. Finlay, L. Eckmann, and K. E. Barrett
Modulation of chloride secretory responses and barrier function of intestinal epithelial cells by the Salmonella effector protein SigD
Am J Physiol Cell Physiol,
October 1, 2004;
287(4):
C939 - C948.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. G.-L. Yue, T. W.-N. Yip, Y. Huang, and W.-H. Ko
Cellular Mechanism for Potentiation of Ca2+-mediated Cl- Secretion by the Flavonoid Baicalein in Intestinal Epithelia
J. Biol. Chem.,
September 17, 2004;
279(38):
39310 - 39316.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. S. Bertelsen, K. E. Barrett, and S. J. Keely
Gs Protein-coupled Receptor Agonists Induce Transactivation of the Epidermal Growth Factor Receptor in T84 Cells: IMPLICATIONS FOR EPITHELIAL SECRETORY RESPONSES
J. Biol. Chem.,
February 20, 2004;
279(8):
6271 - 6279.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
V. Tepavcevic, R. R. Hodges, D. Zoukhri, and D. A. Dartt
Signal Transduction Pathways Used by EGF to Stimulate Protein Secretion in Rat Lacrimal Gland
Invest. Ophthalmol. Vis. Sci.,
March 1, 2003;
44(3):
1075 - 1081.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. J. Keely and K. E. Barrett
p38 mitogen-activated protein kinase inhibits calcium-dependent chloride secretion in T84 colonic epithelial cells
Am J Physiol Cell Physiol,
February 1, 2003;
284(2):
C339 - C348.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Howe, J. Gauldie, and D. M. McKay
TGF-beta effects on epithelial ion transport and barrier: reduced Cl- secretion blocked by a p38 MAPK inhibitor
Am J Physiol Cell Physiol,
December 1, 2002;
283(6):
C1667 - C1674.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. F. McCole, S. J. Keely, R. J. Coffey, and K. E. Barrett
Transactivation of the Epidermal Growth Factor Receptor in Colonic Epithelial Cells by Carbachol Requires Extracellular Release of Transforming Growth Factor-alpha
J. Biol. Chem.,
November 1, 2002;
277(45):
42603 - 42612.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Saksena, R. K. Gill, I. A. Syed, S. Tyagi, W. A. Alrefai, K. Ramaswamy, and P. K. Dudeja
Inhibition of apical Cl-/OH- exchange activity in Caco-2 cells by phorbol esters is mediated by PKCepsilon
Am J Physiol Cell Physiol,
November 1, 2002;
283(5):
C1492 - C1500.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. C. BURESI, A. G. BURET, M. D. HOLLENBERG, and W. K. MacNAUGHTON
Activation of proteinase-activated receptor 1 stimulates epithelial chloride secretion through a unique MAP kinase- and cyclo-oxygenase-dependent pathway
FASEB J,
October 1, 2002;
16(12):
1515 - 1525.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. M. Uribe, D. F. McCole, and K. E. Barrett
Interferon-gamma activates EGF receptor and increases TGF-alpha in T84 cells: implications for chloride secretion
Am J Physiol Gastrointest Liver Physiol,
October 1, 2002;
283(4):
G923 - G931.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. Chang, J. M. Uribe, S. J. Keely, S. Calandrella, and K. E. Barrett
Insulin and IGF-I inhibit calcium-dependent chloride secretion by T84 human colonic epithelial cells
Am J Physiol Gastrointest Liver Physiol,
July 1, 2001;
281(1):
G129 - G137.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Bali, J. Lipecka, A. Edelman, and J. Fritsch
Regulation of ClC-2 chloride channels in T84 cells by TGF-{alpha}
Am J Physiol Cell Physiol,
June 1, 2001;
280(6):
C1588 - C1598.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. E. S. Kahn, A. Senderowicz, E. A. Sausville, and K. E. Barrett
Possible Mechanisms of Diarrheal Side Effects Associated with the Use of a Novel Chemotherapeutic Agent, Flavopiridol
Clin. Cancer Res.,
February 1, 2001;
7(2):
343 - 349.
[Abstract]
[Full Text]
|
 |
|

|
 |

|
 |
 
C.-C. Tsao, J. Foley, S. J. Coulter, R. Maronpot, D. C. Zeldin, and J. A. Goldstein
CYP2C40, a Unique Arachidonic Acid 16-Hydroxylase, Is the Major CYP2C in Murine Intestinal Tract
Mol. Pharmacol.,
August 1, 2000;
58(2):
279 - 287.
[Abstract]
[Full Text]
|
 |
|

|
 |

|
 |
 
D. C. Devor, R. J. Bridges, and J. M. Pilewski
Pharmacological modulation of ion transport across wild-type and Delta F508 CFTR-expressing human bronchial epithelia
Am J Physiol Cell Physiol,
August 1, 2000;
279(2):
C461 - C479.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. L. Dickson, T. D. Conner, and T. W. Ecay
Inhibition of phosphatidylinositol 3-kinase does not alter forskolin-stimulated Cl- secretion by T84 cells
Am J Physiol Cell Physiol,
May 1, 2000;
278(5):
C865 - C872.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. J. Keely, S. O. Calandrella, and K. E. Barrett
Carbachol-stimulated Transactivation of Epidermal Growth Factor Receptor and Mitogen-activated Protein Kinase in T84 Cells Is Mediated by Intracellular Ca2+, PYK-2, and p60src
J. Biol. Chem.,
April 21, 2000;
275(17):
12619 - 12625.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. J. Keely and K. E. Barrett
ErbB2 and ErbB3 Receptors Mediate Inhibition of Calcium-dependent Chloride Secretion in Colonic Epithelial Cells
J. Biol. Chem.,
November 19, 1999;
274(47):
33449 - 33454.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. L. Blazer-Yost, S. I. Helman, K. D. Lee, and C. J. Vlahos
Phosphoinositide 3-kinase is required for aldosterone-regulated sodium reabsorption
Am J Physiol Cell Physiol,
September 1, 1999;
277(3):
C531 - C536.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D M McKAY and A W BAIRD
Cytokine regulation of epithelial permeability and ion transport
Gut,
February 1, 1999;
44(2):
283 - 289.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. E. Galan
Interactions of Salmonella with host cells: Encounters of the closest kind
PNAS,
November 24, 1998;
95(24):
14006 - 14008.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J.-K. Chen, J. R. Falck, K. M. Reddy, J. Capdevila, and R. C. Harris
Epoxyeicosatrienoic Acids and Their Sulfonimide Derivatives Stimulate Tyrosine Phosphorylation and Induce Mitogenesis in Renal Epithelial Cells
J. Biol. Chem.,
October 30, 1998;
273(44):
29254 - 29261.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. J. Keely, J. M. Uribe, and K. E. Barrett
Carbachol Stimulates Transactivation of Epidermal Growth Factor Receptor and Mitogen-activated Protein Kinase in T84 Cells. IMPLICATIONS FOR CARBACHOL-STIMULATED CHLORIDE SECRETION
J. Biol. Chem.,
October 16, 1998;
273(42):
27111 - 27117.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Buret, M. E. Olson, D. G. Gall, and J. A. Hardin
Effects of Orally Administered Epidermal Growth Factor on Enteropathogenic Escherichia coli Infection in Rabbits
Infect. Immun.,
October 1, 1998;
66(10):
4917 - 4923.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Jiang, G. Sweeney, M. T. Rudolf, A. Klip, A. Traynor-Kaplan, and R. Y. Tsien
Membrane-permeant Esters of Phosphatidylinositol 3,4,5-Trisphosphate
J. Biol. Chem.,
May 1, 1998;
273(18):
11017 - 11024.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. E. Barrett, J. Smitham, A. Traynor-Kaplan, and J. M. Uribe
Inhibition of Ca2+-dependent Cl- secretion in T84 cells: membrane target(s) of inhibition is agonist specific
Am J Physiol Cell Physiol,
April 1, 1998;
274(4):
C958 - C965.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Eckmann, M. T. Rudolf, A. Ptasznik, C. Schultz, T. Jiang, N. Wolfson, R. Tsien, J. Fierer, S. B. Shears, M. F. Kagnoff, et al.
D-myo-Inositol 1,4,5,6-tetrakisphosphate produced in human intestinal epithelial cells in response to Salmonella invasion inhibits phosphoinositide 3-kinase signaling pathways
PNAS,
December 23, 1997;
94(26):
14456 - 14460.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Y. C. Chow, J. M. Uribe, and K. E. Barrett
A Role for Protein Kinase Cepsilon in the Inhibitory Effect of Epidermal Growth Factor on Calcium-stimulated Chloride Secretion in Human Colonic Epithelial Cells
J. Biol. Chem.,
July 7, 2000;
275(28):
21169 - 21176.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 1996 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|