Multiple interactions between receptor protein-tyrosine phosphatase (RPTP) alpha and membrane-distal protein-tyrosine phosphatase domains of various RPTPs.
Receptor protein-tyrosine phosphatase (RPTP) alpha belongs to the large family of receptor protein-tyrosine phosphatases containing two tandem phosphatase domains. Most of the catalytic activity is retained in the first, membrane-proximal domain (RPTPalpha-D1), and little is known about the function of the second, membrane-distal domain (RPTPalpha-D2). We investigated whether proteins bound ... to RPTPalpha using the two-hybrid system and found that the second domain of RPTPsigma interacted with the juxtamembrane domain of RPTPalpha. We confirmed this interaction by co-immunoprecipitation experiments. Furthermore, RPTPalpha not only interacted with RPTPsigma-D2 but also with RPTPalpha-D2, LAR-D2, RPTPdelta-D2, and RPTPmu-D2, members of various RPTP subfamilies, although with different affinities. In the yeast two-hybrid system and in glutathione S-transferase pull-down assays, we show that the RPTP-D2s interacted directly with the wedge structure of RPTPalpha-D1 that has been demonstrated to be involved in inactivation of the RPTPalpha-D1/RPTPalpha-D1 homodimer. The interaction was specific because the equivalent wedge structure in LAR was unable to interact with RPTPalpha-D2 or LAR-D2. In vivo, we show that other interaction sites exist as well, including the C terminus of RPTPalpha-D2. The observation that RPTPalpha, but not LAR, bound to multiple RPTP-D2s with varying affinities suggests a specific mechanism of cross-talk between RPTPs that may regulate their biological function.
Mesh Terms:
Animals, COS Cells, Cell Line, Glutathione Transferase, Humans, Nerve Tissue Proteins, Precipitin Tests, Protein Binding, Protein Structure, Tertiary, Protein Tyrosine Phosphatases, Receptor-Like Protein Tyrosine Phosphatases, Class 2, Receptor-Like Protein Tyrosine Phosphatases, Class 4, Receptor-Like Protein Tyrosine Phosphatases, Class 5, Receptors, Cell Surface, Recombinant Fusion Proteins, Transfection, Two-Hybrid System Techniques
Animals, COS Cells, Cell Line, Glutathione Transferase, Humans, Nerve Tissue Proteins, Precipitin Tests, Protein Binding, Protein Structure, Tertiary, Protein Tyrosine Phosphatases, Receptor-Like Protein Tyrosine Phosphatases, Class 2, Receptor-Like Protein Tyrosine Phosphatases, Class 4, Receptor-Like Protein Tyrosine Phosphatases, Class 5, Receptors, Cell Surface, Recombinant Fusion Proteins, Transfection, Two-Hybrid System Techniques
J. Biol. Chem.
Date: Apr. 28, 2000
PubMed ID: 10777529
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