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J. Biol. Chem., Vol. 275, Issue 38, 29539-29546, September 22, 2000
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From the Although it is generally recognized that cystic
fibrosis transmembrane conductance regulator (CFTR) contains a
PSD-95/Disc-large/ZO-1 (PDZ)-binding motif at its COOH terminus, the
identity of the PDZ domain protein(s) that interact with CFTR is
uncertain, and the functional impact of this interaction is not fully
understood. By using human airway epithelial cells, we show that CFTR
associates with Na+/H+ exchanger
(NHE) type 3 kinase A
regulatory protein (E3KARP), an EBP50/NHE
regulatory factor (NHERF)-related PDZ domain protein. The PDZ
binding motif located at the COOH terminus of CFTR interacts preferentially with the second PDZ domain of E3KARP, with nanomolar affinity. In contrast to EBP50/NHERF, E3KARP is predominantly localized
(>95%) in the membrane fractions of Calu-3 and T84 cells, where CFTR
is located. Moreover, confocal immunofluorescence microscopy of
polarized Calu-3 monolayers shows that E3KARP and CFTR are co-localized
at the apical membrane domain. We also found that ezrin associates with
E3KARP in vivo. Co-expression of CFTR with E3KARP and ezrin
in Xenopus oocytes potentiated cAMP-stimulated CFTR
Cl
E3KARP Mediates the Association of Ezrin and Protein Kinase A
with the Cystic Fibrosis Transmembrane Conductance Regulator in Airway
Cells*
,§,,, and
Department of Cell Biology and Physiology,
University of Pittsburgh School of Medicine,
Pittsburgh, Pennsylvania 15261 and the ¶ Department of Medicine,
Division of Gastroenterology, The Johns Hopkins University School
of Medicine, Baltimore, Maryland 21205
currents. These results support the concept that
E3KARP functions as a scaffold protein that links CFTR to ezrin. Since
ezrin has been shown previously to function as a protein kinase A
anchoring protein, we suggest that one function served by the
interaction of E3KARP with both ezrin and CFTR is to localize protein
kinase A in the vicinity of the R-domain of CFTR. Since ezrin is also an actin-binding protein, the formation of a
CFTR·E3KARP·ezrin complex may be important also in
stabilizing CFTR at the apical membrane domain of airway cells.
*
This work was supported by National Institutes of Health
Grants DK56490 and DK44484 and from the Cystic Fibrosis Foundation.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: Dept. of Cell
Biology and Physiology, University of Pittsburgh School of Medicine, S362 BST, 3500 Terrace St., Pittsburgh, PA 15261. Tel.: 412-648-9498; Fax: 412-648-2004: E-mail: Frizzell+@pitt.edu.
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|
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|
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|
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|
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|
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|
|
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|
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|
|
|
|
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|
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|
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|
|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
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|
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|
|
|
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|
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|
 |
|
 K. Kunzelmann CFTR: Interacting With Everything? Physiology, August 1, 2001; 16(4): 167 - 170. [Abstract] [Full Text] [PDF]
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|
|
|
|
|
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|
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|
|
|
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