The nontransmembrane tyrosine phosphatase PTP-1B localizes to the endoplasmic reticulum via its 35 amino acid C-terminal sequence

Cell. 1992 Feb 7;68(3):545-60. doi: 10.1016/0092-8674(92)90190-n.


We report the first intracellular characterization of an endogenous nontransmembrane protein tyrosine phosphatase (PTP). Using affinity-purified polyclonal antibodies, we have identified PTP-1B as a 50 kd serine phosphoprotein in immunoprecipitation and immunoblotting assays. Surprisingly, indirect immunofluorescence experiments indicate that PTP-1B is localized predominantly in the endoplasmic reticulum (ER). Subcellular fractionation is consistent with this localization and establishes that PTP-1B is tightly associated with microsomal membranes, with its phosphatase domain oriented towards the cytoplasm. The C-terminal 35 amino acids of PTP-1B are both necessary and sufficient for targeting to the ER. The finding of a tyrosine phosphatase on the ER suggests new possibilities for cellular events controlled by tyrosine phosphorylation.

Publication types

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

MeSH terms

  • Animals
  • Antibodies / isolation & purification
  • Base Sequence
  • Cell Fractionation
  • Cell Line
  • Chlorocebus aethiops
  • Cloning, Molecular
  • Endoplasmic Reticulum / enzymology*
  • HeLa Cells / chemistry
  • Humans
  • Immunoblotting
  • Membrane Proteins / analysis*
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Plasmids
  • Precipitin Tests
  • Protein Sorting Signals / analysis*
  • Protein Tyrosine Phosphatases / analysis*
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / immunology
  • Rabbits


  • Antibodies
  • Membrane Proteins
  • Protein Sorting Signals
  • Protein Tyrosine Phosphatases