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 C gamma (PLC gamma) by the platelet-derived growth factor-beta receptor (PDGF beta R) is regulated by the SH2 domain-containing protein tyrosine phosphatase PTP2C (also known as SHP-2). When co-expressed in S. pombe, PTP2C abolished PDGF beta R autophosphorylation as well as its ability to phosphorylate and activate PLC gamma. Inhibition of PDGF beta R signalling by PTP2C appears specific insofar that PTP1C, a close homologue of PTP2C, does not suppress activation of either PDGF beta R or PLC gamma. Surprisingly, an inactive PTP2C mutant (C459S), which dephosphorylates neither PDGF beta R nor PLC gamma, remains fully effective as an inhibitor of [H-3]inositol phosphate generation indicating that negative regulation is at least in part independent of catalytic activity, This contrasts with PLC gamma 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 PDGF beta R and its signalling to PLC gamma. (C) 1998 Federation of European Biochemical Societies.