The transmembrane protein tyrosine phosphatase RPTPsigma 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 RPTPsigma but not RPTPalpha or the SH2-domain PTP SHP-1 exhibited elevated activity towards EGF receptor in G(M3)-treated cells. The possible relevance of RPTPsigma for regulation of EGF receptor signaling activity was further explored in stable A431 cells lines inducibly expressing RPTPsigma or RPTPsigma antisense RNA. RPTPsigma expression clearly reduced EGF receptor phosphorylation. Also, soft agar colony formation of respective cell lines was reduced upon RPTPsigma expression whereas RPTPsigma antisense RNA expression augmented both, EGF receptor phosphorylation and soft agar colony formation. In addition, RPTPsigma antisense RNA expression rendered A431 cells resistant to inhibition of EGF receptor phosphorylation by G(M3). We propose that RPTPsigma 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).