Phenotypic analyses of PTP-PEST null cells and gene targeting of its substrate, p130cas

To understand the physiological role of the protein tyrosine phosphatase (PTP) PEST, the phenotypes of PTP-PEST (--/--) mouse fibroblasts have been studied PTP-PEST was shown to translocate to the membrane periphery following stimulation by the extracellular matrix protein fibronectin, and to play a role in cell migration, spreading, and cytokinesis. For this action, PTP-PEST was shown to regulate the phosphorylation levels of p130cas, paxillin, FAK and PSTPIP, and their association with SH2 domain-containing proteins like Src and Crk. From these proteins, p130cas is known to be a direct substrate. Experiments for the obtention of p130cas (--/--) embryos and cell lines have also been initiated, up to the generation of adult chimeric animals. In the process, a genomic fragment of p130cas containing a C-terminal exon has been cloned and analysed