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

Attenuation of epidermal growth factor receptor signaling by the ganglioside G(M3) has previously been found to involve activation of an unknown protein-tyrosine phosphatase (PTP). In transient expression experiments we tested different PTPs for activation towards EGF receptor by G(M3). The transmembrane PTP RPTP sigma but not RPTP alpha or the SH2-domain PTP SHP-1 exhibited elevated activity towards EGF receptor in G(M3)-treated cells. The possible relevance of RPTP sigma for regulation of EGF receptor signaling activity was further explored in stable A431 cells lines inducibly expressing RPTP sigma or RPTP sigma antisense RNA. RPTP sigma expression clearly reduced EGF receptor phosphorylation, Also, soft agar colony formation of respective cell lines was reduced upon RPTP sigma expression whereas RPTP sigma antisense RNA expression augmented both, EGF receptor phosphorylation and soft agar colony formation. In addition, RPTP sigma antisense RNA expression rendered A431 cells resistant to inhibition of EGF receptor phosphorylation by G(M3). We propose that RPTP sigma participates in EGF receptor dephosphorylation in A431 cells, becomes activated by G(M3) via an unknown mechanism and is thereby capable to mediate attenuation of EGF receptor phosphorylation by G(M3).