Summary
Receptor-like protein tyrosine phosphatases (RPTPases) comprise an extracellular ligand-binding region, a transmembrane domain, and as a rule two cytoplasmic tyrosine phosphatase domains. In vitro studies using the cytoplasmic parts of RPTPases and artificial substrates have suggested that the first, membrane proximal phosphatase domain exhibits catalytic activity, whereas the second, C-terminal phosphatase domain may regulate the phosphatase activity of the first domain. Further studies, however, are hampered by the fact that RPTPase-specific ligands and substrates still remain to be identified. Also, the complexity of transmembrane signalling is difficult to mimick in vitro. To circumvent these problems, the individual functions of the two phosphatase domains in RPTPases can be studied in vivo by means of homologous recombination in mouse embryonic stem (ES) cells. Here, we decribe the use of ’double replacement’ gene targeting in mouse embryonic stem cells to generate cell and animal models for studying the individual role of both phosphatase domains of the RPTPase Leukocyte common Antigen-Related molecule LAR. In addition, exploiting the process of gene conversion, LAR-negative ES cells were generated to enable structure-function analysis of LAR mutants on a null background.
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Schaapveld, R., Schepens, J., Oerlemans, F., Streuli, M., Wieringa, B., Hendriks, W. (1995). Gene Targeting of the Receptor-Like Protein Tyrosine Phosphatase Lar by Homologous Recombination in Mouse Embryonic Stem Cells. In: Packer, L., Wirtz, K.W.A. (eds) Signalling Mechanisms — from Transcription Factors to Oxidative Stress. NATO ASI Series, vol 92. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-79675-3_29
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DOI: https://doi.org/10.1007/978-3-642-79675-3_29
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