Interaction of the protein phosphatase 2A with the regulatory domain of the cystic fibrosis transmembrane conductance regulator channel

被引:17
作者
Vastiau, A
Cao, LS
Jaspers, M
Owsianik, G
Janssens, V
Cuppens, H
Goris, J
Nilius, B
Cassiman, JJ
机构
[1] Katholieke Univ Leuven, Dept Human Genet, Div Human Mutat & Polymorphisms, B-3000 Louvain, Belgium
[2] Katholieke Univ Leuven, Dept Mol Cell Biol, Div Physiol, B-3000 Louvain, Belgium
[3] Katholieke Univ Leuven, Dept Mol Cell Biol, Div Biochem, B-3000 Louvain, Belgium
关键词
CFTR; PP2A; protein-protein interaction;
D O I
10.1016/j.febslet.2005.04.079
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A direct interaction of the regulatory domain (R domain) of the cystic fibrosis transmembrane conductance regulator protein (CFTR) with PR65, a regulatory subunit of the protein phosphatase 2A (PP2A), was shown in yeast two hybrid, pull-down and co-immunoprecipitation experiments. The R domain could be dephosphorylated by PP2A in vitro. Overexpression of the interacting domain of PR65 in Caco-2 cells, as well as treatment with okadaic acid, showed a prolonged deactivation of the chloride channel. Taken together our results show a direct and functional interaction between CFTR and PP2A. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:3392 / 3396
页数:5
相关论文
共 17 条
[1]  
BERGER HA, 1993, J BIOL CHEM, V268, P2037
[2]   IMPROVED METHOD FOR HIGH-EFFICIENCY TRANSFORMATION OF INTACT YEAST-CELLS [J].
GIETZ, D ;
STJEAN, A ;
WOODS, RA ;
SCHIESTL, RH .
NUCLEIC ACIDS RESEARCH, 1992, 20 (06) :1425-1425
[3]   The structure of the protein phosphatase 2A PR65/A subunit reveals the conformation of its 15 tandemly repeated HEAT motifs [J].
Groves, MR ;
Hanlon, N ;
Turowski, P ;
Hemmings, BA ;
Barford, D .
CELL, 1999, 96 (01) :99-110
[4]   IMPROVED PATCH-CLAMP TECHNIQUES FOR HIGH-RESOLUTION CURRENT RECORDING FROM CELLS AND CELL-FREE MEMBRANE PATCHES [J].
HAMILL, OP ;
MARTY, A ;
NEHER, E ;
SAKMANN, B ;
SIGWORTH, FJ .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1981, 391 (02) :85-100
[5]  
HARDIE DG, 1991, METHOD ENZYMOL, V201, P469
[6]   FUNCTIONALLY DISTINCT PHOSPHO-FORMS UNDERLIE INCREMENTAL ACTIVATION OF PROTEIN-KINASE REGULATED CL- CONDUCTANCE IN MAMMALIAN HEART [J].
HWANG, TC ;
HORIE, M ;
GADSBY, DC .
JOURNAL OF GENERAL PHYSIOLOGY, 1993, 101 (05) :629-650
[7]   Protein phosphatase 2A: a highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling [J].
Janssens, V ;
Goris, J .
BIOCHEMICAL JOURNAL, 2001, 353 :417-439
[8]   Differential regulation of single CFTR channels by PP2C, PP2A, and other phosphatases [J].
Luo, JX ;
Pato, MD ;
Riordan, JR ;
Hanrahan, JW .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 1998, 274 (05) :C1397-C1410
[9]   Deactivation of CFTR-Cl conductance by endogenous phosphatases in the native sweat duct [J].
Reddy, MM ;
Quinton, PM .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 1996, 270 (02) :C474-C480
[10]  
RIORDAN JR, 1989, SCIENCE, V245, P1066