14–3-3, set me free
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《细胞学杂志》
Goldstein/Elsevier
The protein that does everything, 14–3-3, has now been shown to direct traffic. Ita O'Kelly, Steve Goldstein, and colleagues (Yale University, New Haven, CT) find that 14–3-3 can displace ?-COP from various proteins, thus freeing them from retention in the ER and leading to surface expression.
Goldstein set out to find proteins interacting with the COOH terminus of a K+ leak channel, KCNK3, and came up with a surprise: 14–3-3?. The group also found that KCNK3 binds ?-COP, the COP1 retrieval protein, via a known dibasic motif. Binding of 14–3-3? and ?-COP to KCNK3 was mutually exclusive. Deletion of the last residue of the 14–3-3? binding site led to retention of all KCNK3 protein in the ER, but surface expression was rescued by a further mutation of the dibasic ?-COP binding sequence.
A similar system was demonstrated for another leak channel, an acetylcholine receptor subunit, and an MHC-associated protein. Others had individual clues in these systems about trafficking and the binding of 14–3-3 and ?-COP, but Goldstein's group is the first to put the whole story together.
For KCNK3, hormonal signals that turn on PKA may trigger the binding of 14–3-3? to the phosphorylated channel subunit, thus increasing surface expression and decreasing the excitability of the cell. Goldstein now wants to know if such a mechanism for controlling surface expression levels is common, and what proteins act with 14–3-3 to release the grip of ER retention.
Reference:
O'Kelly, I., et al. 2002. Cell. 111:577–588.(14–3-3 turns ER retention (left) into su)
The protein that does everything, 14–3-3, has now been shown to direct traffic. Ita O'Kelly, Steve Goldstein, and colleagues (Yale University, New Haven, CT) find that 14–3-3 can displace ?-COP from various proteins, thus freeing them from retention in the ER and leading to surface expression.
Goldstein set out to find proteins interacting with the COOH terminus of a K+ leak channel, KCNK3, and came up with a surprise: 14–3-3?. The group also found that KCNK3 binds ?-COP, the COP1 retrieval protein, via a known dibasic motif. Binding of 14–3-3? and ?-COP to KCNK3 was mutually exclusive. Deletion of the last residue of the 14–3-3? binding site led to retention of all KCNK3 protein in the ER, but surface expression was rescued by a further mutation of the dibasic ?-COP binding sequence.
A similar system was demonstrated for another leak channel, an acetylcholine receptor subunit, and an MHC-associated protein. Others had individual clues in these systems about trafficking and the binding of 14–3-3 and ?-COP, but Goldstein's group is the first to put the whole story together.
For KCNK3, hormonal signals that turn on PKA may trigger the binding of 14–3-3? to the phosphorylated channel subunit, thus increasing surface expression and decreasing the excitability of the cell. Goldstein now wants to know if such a mechanism for controlling surface expression levels is common, and what proteins act with 14–3-3 to release the grip of ER retention.
Reference:
O'Kelly, I., et al. 2002. Cell. 111:577–588.(14–3-3 turns ER retention (left) into su)