Importance of the G protein gamma subunit in activating G protein-coupled inward rectifier K(+) channels.
The G protein-coupled inward rectifier K(+) channel (GIRK) is activated by direct interaction with the heterotrimeric GTP-binding protein betagamma subunits (Gbetagamma). However, the precise role of Gbeta and Ggamma in GIRK activation remains to be elucidated. Using transient expression of GIRK1, GIRK2, Gbeta1, and Ggamma2 in human embryonic kidney 293 cells, we show that C-terminal mutants of Gbeta1, which do not bind to Ggamma2, are still able to associate with GIRK, but these mutants are unable to induce activation of GIRK channels. In contrast, other C-terminal mutants of Gbeta1 that bind to Ggamma2, are capable of activating the GIRK channel. These results suggest that Ggamma plays a more important role than that of an anchoring device for the Gbetagamma-induced GIRK activation.
Kawano
T
T
Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama, Japan.
Chen
L
L
Watanabe
S Y
SY
Yamauchi
J
J
Kaziro
Y
Y
Nakajima
Y
Y
Nakajima
S
S
Itoh
H
H
D002460:Cell Line; D018076:DNA, Complementary / Q000302:isolation & purification; D004789:Enzyme Activation; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D015870:Gene Expression; D020962:Heterotrimeric GTP-Binding Proteins; D006801:Humans; D015151:Immunoblotting; D009154:Mutation; D016133:Polymerase Chain Reaction; D015221:Potassium Channels / Q000737:chemistry* / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying; D014162:Transfection
D018076:DNA, Complementary; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C118981:G-protein Beta gamma; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D019204:GTP-Binding Proteins; D020962:Heterotrimeric GTP-Binding Proteins