Modulation of the Ca(2+)-activated Cl(-) channel by 14-3-3epsilon.
We have previously reported an association of 14-3-3epsilon isoform with calmodulin. Using the voltage-clamp technique, the present study investigated the potential role of 14-3-3 in modulating the Ca(2+)-activated Cl(-) channel (CaCC) endogenously expressed in Xenopus oocytes. Injection of 14-3-3epsilon antisense oligodeoxynucleotides resulted in potentiation of the ionomycin-induced Cl(-) current, while 14-3-3 peptide and calmodulin inhibitor, W13, suppressed the antisense-potentiated current. The data suggest that 14-3-3epsilon plays an inhibitory role in modulating the CaCC by interacting with the calmodulin-dependent pathway. The potential role of 14-3-3epsilon in other tissues and its therapeutic potential for cystic fibrosis are discussed.
Chan
H C
HC
Epithelial Cell Biology Research Centre, Department of Physiology, Faculty of Medicine, Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.
Wu
W L
WL
So
S C
SC
Chung
Y W
YW
Tsang
L L
LL
Wang
X F
XF
Yan
Y C
YC
Luk
S C
SC
Siu
S S
SS
Tsui
S K
SK
Fung
K P
KP
Lee
C Y
CY
Waye
M M
MM
D048948:14-3-3 Proteins; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D065101:Chloride Channel Agonists; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase; D014981:Xenopus
D048948:14-3-3 Proteins; D065101:Chloride Channel Agonists; D018118:Chloride Channels; D016376:Oligonucleotides, Antisense; D011506:Proteins; D015759:Ionomycin; D014446:Tyrosine 3-Monooxygenase; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D002118:Calcium