AN ALTERNATIVE ROLE FOR THE SRC-HOMOLOGY-DOMAIN-CONTAINING PHOSPHOTYROSINE PHOSPHATASE (SH-PTP2) IN REGULATING EPIDERMAL-GROWTH-FACTOR-DEPENDENT CELL-GROWTH

The association of the src homology 2 (SH2) domain-containing tyrosine phosphatase (SH-PTP2) with the activated epidermal growth factor (EGF ) and platelet-derived growth factor receptors, as well as the insulin receptor substrate 1 and growth-factor-receptor-bound protein 2 and i ts intrinsic tyrosine phosphatase activity suggests an important role for this phosphatase in signal transduction. Previous studies have sho wn a positive role for SH-PTP2 in growth-factor-mediated cell signalin g. We show here that SH-PTP2 can also function to negatively regulate EGF-mediated signal transduction in the human glioma cell line SNB19. We demonstrate this by showing that, in SNB19 cells, which lack the ab ility to proliferate in response to EGF but retain the ability to bind EGF and also activate the EGF receptor as well as allow for the assoc iation of SH-PTP2 with the phosphorylated receptor, stable overexpress ion of an interfering SH-PTP2 mutant can restore the ability of these cells to proliferate in response to EGF.