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Goldstein/Elsevier
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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.5 E7 v9 {. {8 O
( U& r4 n0 n- O% k7 X8 p* K7 TGoldstein 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.
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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.) ?$ W3 q5 |: U! z
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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.1 j) Q3 r8 i$ Y. Q2 X! ~
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O'Kelly, I., et al. 2002. Cell. 111:577–588.(14–3-3 turns ER retention (left) into su) |
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发表于 2009-3-6 00:18
发表于 2015-5-27 13:42
