标题: 14–3-3, set me free [打印本页] 作者: 杨柳 时间: 2009-3-6 00:18 标题: 14–3-3, set me free
Goldstein/Elsevier6 i. [' ~6 @5 B1 T; {) k
* A; {& n, Z; [6 H* C* o7 `% e' cThe 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. $ q' q! f L; [, T {' Y- p; w0 L6 D$ i8 u" V* p
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. & i t ]3 x, S4 o ) H6 A5 H' w$ ^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. - j& k- R v8 a6 R4 u7 V3 f$ [. f; e4 z, y3 z. I# H3 W8 d$ J- J
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. " X0 i! Z6 u- e4 c5 L, c0 l4 d* _/ b0 K+ p, Y! B! P( c
Reference: $ l4 q5 s% i8 k( r+ ~9 p ! w' J; L; @# i# R7 H/ a% v* wO'Kelly, I., et al. 2002. Cell. 111:577–588.(14–3-3 turns ER retention (left) into su)作者: xuguofeng 时间: 2015-5-27 13:42