cells, CD4(+) T cells development is inhibited. PTPkappa likely regulates T-cell development by positively regulating ERK1/2 phosphorylation via the regulation of MEK1/2 and c-Raf phosphorylation. Cadherin-catenin signaling PTPkappa is localized to cell-cell contact sites, where it colocalizes and co-immunoprecipitates with β-catenin and plakoglobin/γ-catenin β-catenin may be a PTPkappa substrate. The presence of full-length PTPkappa in melanoma cells decreases the level of free-cytosolic β-catenin, which consequently reduces the level of nuclear β-catenin and reduces the expression of the β-catenin-regulated genes, cyclin D1 and c-myc. Expression of ful-length PTPkappa in melanoma cells that normally lack its expression results in reduced cell migration and cell proliferation. Because the presence of PTPkappa at the cell membrane was shown to sequester β-catenin to the plasma membrane, these data suggest that one mechanism whereby PTPkappa functions as a tumor suppressor is by regulating the intracellular localization of free-β-catenin. The intracellular fragments of PTPkappa, PΔE and PIC, are catalytically active, and can also dephosphorylate β-catenin. Tyrosine phosphorylated β-catenin translocates to the cell nucleus and activates TCF-mediated transcription to promote cell proliferation and migration. While full-length PTPkappa antagonizes TCF-mediated transcription, the PIC fragment augments it, perhaps by regulating other proteins in TCF-mediated transcription. This suggests that phosphatase activity of the PIC fragment opposes that of full-length PTPkappa. PTPkappa interacts by co-immunoprecipitation with E-cadherin, α-catenin and β-catenin in pancreatic acinar cells prior to the dissolution of adherens junctions in a rat model of pancreatitis. The authors suggest that the presence of PTPkappa at the plasma membrane in association with the cadherin/catenin complex is important for the maintenance of adherens junction in pancreatic acinar cells, much as it was suggested above in melanoma cells. EGFR signaling Use of short interfering RNA (siRNA) of PTPkappa to reduce PTPkappa protein expression in the mammary epithelial cell line, MCF10A, resulted in increased cell proliferation. PTPkappa expression, conversely, was demonstrated to reduce cell proliferation in Chinese hamster ovary cells. The mechanism proposed to explain the influence of PTPkappa on cell proliferation is via PTPkappa dephosphorylation of the EGFR on tyrosines 1068 and 1173 directly. The reduction of PTPkappa expression in CHO cells with PTPkappa siRNA increased EGFR phosphorylation. Therefore, the hypothesis is that PTPkappa functions as a tumor suppressor gene by dephosphorylating and inactivating EGFR. In addition, glycosylation by N-acetylglucosaminyltransferase-V (GnT-V) has been shown to reduce full-length PTPkappa expression, likely via increasing its cleavage. This aberrant glycosylation has been shown to increase the phosphorylation