The transmembrane protein tyrosine phosphatase RPTP sigma modulates signaling of the epidermal growth factor receptor in A431 cells

Attenuation of epidermal growth factor receptor signaling by the gangliosid e G(M3) has previously been found to involve activation of an unknown prote in-tyrosine phosphatase (PTP). In transient expression experiments we teste d different PTPs for activation towards EGF receptor by G(M3). The transmem brane PTP RPTP sigma but not RPTP alpha or the SH2-domain PTP SHP-1 exhibit ed elevated activity towards EGF receptor in G(M3)-treated cells. The possi ble relevance of RPTP sigma for regulation of EGF receptor signaling activi ty was further explored in stable A431 cells lines inducibly expressing RPT P sigma or RPTP sigma antisense RNA. RPTP sigma expression clearly reduced EGF receptor phosphorylation, Also, soft agar colony formation of respectiv e cell lines was reduced upon RPTP sigma expression whereas RPTP sigma anti sense RNA expression augmented both, EGF receptor phosphorylation and soft agar colony formation. In addition, RPTP sigma antisense RNA expression ren dered A431 cells resistant to inhibition of EGF receptor phosphorylation by G(M3). We propose that RPTP sigma participates in EGF receptor dephosphory lation in A431 cells, becomes activated by G(M3) via an unknown mechanism a nd is thereby capable to mediate attenuation of EGF receptor phosphorylatio n by G(M3).