Transmembrane transforming growth factor-alpha tethers to the PDZ domain-containing, Golgi membrane-associated protein p59/GRASP55

EMBO J. 2000 Dec 1;19(23):6427-39. doi: 10.1093/emboj/19.23.6427.


Transforming growth factor-alpha (TGF-alpha) and related proteins represent a family of transmembrane growth factors with representatives in flies and worms. Little is known about the transport of TGF-alpha and other transmembrane growth factors to the cell surface and its regulation. p59 was purified as a cytoplasmic protein, which at endogenous levels associates with transmembrane TGF-alpha. cDNA cloning of p59 revealed a 452 amino acid sequence with two PDZ domains. p59 is myristoylated and palmitoylated, and associates with the Golgi system, where it co-localizes with TGF-alpha. Its first PDZ domain interacts with the C-terminus of transmembrane TGF-alpha and select transmembrane proteins. p59 is the human homolog of GRASP55, which is structurally related to GRASP65. GRASP55 and GRASP65 have been shown to play a role in stacking of the Golgi cisternae in vitro. C-terminal mutations of transmembrane TGF-alpha, which decrease or abolish the interaction with p59, also strongly impair cell surface expression of TGF-alpha. Our observations suggest a role for membrane tethering of p59/GRASP55 to select transmembrane proteins, including TGF-alpha, in maturation and transport to the cell surface.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Western
  • CHO Cells
  • Cell Line
  • Cell Membrane / metabolism*
  • Chromatography, High Pressure Liquid
  • Cloning, Molecular
  • Cricetinae
  • Cytoplasm / chemistry
  • DNA, Complementary / metabolism
  • Electrophoresis, Gel, Two-Dimensional
  • Electrophoresis, Polyacrylamide Gel
  • Fluorescent Antibody Technique
  • Golgi Apparatus / metabolism*
  • Golgi Matrix Proteins
  • HeLa Cells
  • Humans
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Molecular Sequence Data
  • Myristic Acids / metabolism
  • Palmitic Acids / metabolism
  • Plasmids / metabolism
  • Precipitin Tests
  • Protein Binding
  • Protein Structure, Tertiary
  • Protein Transport
  • Sequence Homology, Amino Acid
  • Transfection
  • Transforming Growth Factor alpha / physiology*


  • DNA, Complementary
  • GORASP1 protein, human
  • GORASP2 protein, human
  • Golgi Matrix Proteins
  • Membrane Proteins
  • Myristic Acids
  • Palmitic Acids
  • Transforming Growth Factor alpha