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

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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Amino Acid Motifs, Amino Acid Sequence, Antigens, Neoplasm, Carrier Proteins, Hela Cells, Humans, Membrane Glycoproteins, Microscopy, Fluorescence, Molecular Sequence Data, Neoplasm Metastasis, Neuropeptides, Precipitin Tests, Protein Structure, Tertiary, Sequence Homology, Amino Acid, Two-Hybrid System Techniques, Yeasts
Biochem. Biophys. Res. Commun.
Date: Jan. 25, 2002
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