Forward transport. 14-3-3 binding overcomes retention in endoplasmic reticulum by dibasic signals

Cell. 2002 Nov 15;111(4):577-88. doi: 10.1016/s0092-8674(02)01040-1.


Proteins with dibasic retention motifs are subject to retrograde transport to endoplasmic reticulum (ER) by COPI-coated vesicles. As forward transport requires escape from ER retention, general release mechanisms have been expected. Here, KCNK3 potassium channels are shown to bear two cytoplasmic trafficking motifs: an N-terminal dibasic site that binds beta-COP to hold channels in ER and a C-terminal "release" site that binds the ubiquitous intracellular regulator 14-3-3beta on a nonclassical motif in a phosphorylation-dependent fashion to suppress beta-COP binding and allow forward transport. The strategy appears to be common. The major histocompatibility antigen class II-associated invariant chain Iip35 exhibits dibasic retention, carries a release motif, and shows mutually exclusive binding of beta-COP and 14-3-3beta on adjacent N-terminal sites. Other retained proteins are demonstrated to carry functional 14-3-3beta release motifs.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 14-3-3 Proteins
  • Amino Acid Motifs
  • Animals
  • Binding Sites
  • COS Cells
  • Chlorocebus aethiops
  • Coatomer Protein / metabolism*
  • Endoplasmic Reticulum / metabolism*
  • Humans
  • Nerve Tissue Proteins
  • Peptides / metabolism
  • Potassium Channels / genetics
  • Potassium Channels / metabolism*
  • Potassium Channels, Tandem Pore Domain
  • Protein Transport
  • Rats
  • Tyrosine 3-Monooxygenase / genetics
  • Tyrosine 3-Monooxygenase / metabolism*
  • Valine / metabolism


  • 14-3-3 Proteins
  • Coatomer Protein
  • Nerve Tissue Proteins
  • Peptides
  • Potassium Channels
  • Potassium Channels, Tandem Pore Domain
  • YWHAB protein, human
  • potassium channel subfamily K member 3
  • Tyrosine 3-Monooxygenase
  • Valine