A negative regulatory function for the protein tyrosine phosphatase PTP2C revealed by reconstruction of platelet-derived growth factor receptor signalling in Schizosaccharomyces pombe.

We have exploited reconstitution in the fission yeast Schizosaccharomyces pombe to investigate how activation of phospholipase Cγ (PLCγ) by the platelet-derived growth factor-β receptor (PDGFβR) is regulated by the SH2 domain-containing protein tyrosine phosphatase PTP2C (also known as SHP-2). When co-expressed in S. pombe, PTP2C abolished PDGFβR autophosphorylation as well as its ability to phosphorylate and activate PLCγ. Inhibition of PDGFβR signalling by PTP2C appears specific insofar that PTP1C, a close homologue of PTP2C, does not suppress activation of either PDGFβR or PLCγ. Surprisingly, an inactive PTP2C mutant (C459S), which dephosphorylates neither PDGFβR nor PLCγ, remains fully effective as an inhibitor of [3H]inositol phosphate generation indicating that negative regulation is at least in part independent of catalytic activity. This contrasts with PLCγ activation by c-Src which, although blocked by active PTP2C, is not inhibited by the mutant PTP2C C459S. These observations indicate that in addition to a reported positive role relaying trophic signals, PTP2C can also exert a negative effect on the PDGFβR and its signalling to PLCγ.