5T4 interacts with TIP-2/GIPC, a PDZ protein, with implications for metastasis

Biochem Biophys Res Commun. 2002 Jan 25;290(3):1030-6. doi: 10.1006/bbrc.2001.6288.


Overexpression of the 5T4 transmembrane glycoprotein can have marked effects on both the actin cytoskeleton and cell migration. Using a yeast two-hybrid approach, we describe a novel interaction between 5T4 and TIP-2/GIPC, a cytoplasmic interacting protein containing a PDZ domain. The cytoplasmic tail of 5T4 contains a class I PDZ-binding motif (Ser-Asp-Val) and we demonstrate that this region, in particular the terminal valine, is required for 5T4 interaction with TIP-2/GIPC. HeLa cells expressing hemagglutinin-tagged TIP-2/GIPC (HA-TIP-2/GIPC) have an altered distribution of endogenous 5T4, which colocalizes with HA-TIP-2/GIPC, thus supporting an interaction. Furthermore, TIP-2/GIPC can be coimmunoprecipitated with 5T4 from HeLa cell lysates. Identification of the 5T4 and TIP-2/GIPC interaction provides the first link between 5T4 and the actin cytoskeleton. Since other proteins, like 5T4, associate with TIP-2/GIPC and are linked with cancer, we explore the possibility that TIP-2/GIPC may be a common factor involved in the cancer process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Antigens, Neoplasm / chemistry
  • Antigens, Neoplasm / metabolism*
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • HeLa Cells
  • Humans
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / metabolism*
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Neoplasm Metastasis
  • Neuropeptides / chemistry
  • Neuropeptides / metabolism*
  • Precipitin Tests
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Two-Hybrid System Techniques
  • Yeasts / genetics


  • Adaptor Proteins, Signal Transducing
  • Antigens, Neoplasm
  • Carrier Proteins
  • GIPC1 protein, human
  • Membrane Glycoproteins
  • Neuropeptides
  • trophoblastic glycoprotein 5T4, human