标题: A trip to the ER [打印本页] 作者: 杨柳 时间: 2009-3-6 00:18 标题: A trip to the ER
Bastiaens/AAAS 9 M0 @7 n) a3 J2 y - K( }3 {5 P2 \ jDephosphorylation of activated receptor tyrosine kinases (RTKs) involves a trip to the surface of the ER, according to new results from Benjamin Neel (Beth Israel-Deaconess Medical Center, Boston, MA), Philippe Bastiaens (EMBL, Heidelberg, Germany), and colleagues. 3 @3 |: M' L9 t4 B( O J# l * k0 m9 F( F0 P" ^3 T8 N$ hThe new results demonstrate that the protein tyrosine phosphatase PTP1B dephosphorylates RTKs at distinct locations on the cytoplasmic face of the ER. Although it was shown that the ER-localized PTP1B interacts with and can dephosphorylate several growth factor receptors, Neel says it was generally thought that dephosphorylation at this location was simply reversing gratuitous autophosphorylation during RTK synthesis in the ER.The groups demonstrated, however, that upon growth factor activation, two RTKs, EGFR and PDGFR, move from the plasma membrane and pass by the ER. A high percentage of these internalized RTKs interacted with PTP1B. The authors used FRET to visualize this interaction in cells by engineering a PTP1B mutant that traps its RTK substrate. 0 E5 Q% f' G. i. a' V& ?5 q3 k8 V+ e1 F" R! q7 Q
The distinct locations of kinase activation by phosphorylation (at the plasma membrane) and dephosphorylation by PTP1B (at the ER) may provide a necessary time delay between turning on and off signaling receptors, thus regulating the lifespan of an active RTK signal. Dephosphorylation could deactivate receptors before they are either sent back to the plasma membrane or to degradative lysosomes. ( z- \3 K6 A- T0 u" `0 E _ Z / K4 @8 f0 S$ H/ f* m( J9 b }Reference:! r' N g6 \" T ?
y$ N3 s- u& T! V% g4 E" MHaj, F., et al. 2002. Science. 295:1708–1711.(EGFR and PTP1B interact at the ER (green)作者: 命运的宠儿 时间: 2015-6-13 17:03