A trip to the ER

Dephosphorylation 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.

The 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...