Section 11
Chapter 10,807

Importance of the G protein gamma subunit in activating G protein-coupled inward rectifier K (+) channels

Kawano, T.; Chen, L.; Watanabe, S.Y.; Yamauchi, J.; Kaziro, Y.; Nakajima, Y.; Nakajima, S.; Itoh, H.

Febs Letters 463(3): 355-359


ISSN/ISBN: 0014-5793
PMID: 10606753
DOI: 10.1016/s0014-5793(99)01656-7
Accession: 010806491

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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.

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